scholarly journals Effects of a Chinese Herbal Medicine, Guan-Jen-Huang (Aeginetia indicaLinn.), on Renal Cancer Cell Growth and Metastasis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Yu-Huei Liu ◽  
Meng-Luen Li ◽  
Meng-Yu Hsu ◽  
Ya-Yueh Pang ◽  
I-Ling Chen ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Renal Cancer ◽  
Cellular Proliferation ◽  
Synergistic Effects ◽  
Umbilical Vein ◽  
Chinese Herb ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Intercellular Adhesion Molecule ◽  
Migration And Invasion

Aeginetia indicaLinn. (Guan-Jen-Huang, GJH), a traditional Chinese herb, has the potential to be an immunomodulatory agent. The purpose of this study was to explore the effect of GJH in the treatment of renal cancer. Concentration-effect curves for the influence of GJH on cellular proliferation showed a biphasic shape. Besides, GJH had a synergistic effect on cytotoxicity when combined with 5-fluorouracil (5-FU)which may be due to the alternation of the chemotherapeutic agent resistance-related genes and due to the synergistic effects on apoptosis. In addition, treatment with GJH extract markedly reduced 786-O cell adherence to human umbilical vein endothelial cells (HUVECs) and decreased 786-O cell migration and invasion. In a xenograft animal model, GJH extract had an inhibitory effect on tumor cell-induced metastasis. Moreover, western blot analysis showed that the expression of intercellular adhesion molecule-1 (ICAM-1) in 786-O cells was significantly decreased by treatment with GJH extract through inactivation of nuclear factor-κB (NF--κB). These results suggest that GJH extract has a synergistic effect on apoptosis induced by chemotherapeutic agents and an inhibitory effect on cell adhesion, migration, and invasion, providing evidence for the use of water-based extracts of GJH as novel alternative therapeutic agents in the treatment of human renal cancer.

scholarly journals Antiproliferative Activity of Combined Biochanin A and Ginsenoside Rh2 on MDA-MB-231 and MCF-7 Human Breast Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2908 ◽  
Author(s):  
Guixing Ren ◽  
Zhenxing Shi ◽  
Cong Teng ◽  
Yang Yao
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Human Breast Cancer ◽  
Synergistic Effects ◽  
Inhibitory Effect ◽  
Biochanin A ◽  
Migration And Invasion ◽  
Ginsenoside Rh2 ◽  
Human Breast ◽  
Mcf 7

Breast cancer is the most frequently diagnosed cancer in women worldwide. The antiproliferative activities of biochanin A (BA) and ginsenoside Rh2 were determined by evaluating their inhibitory effect on MDA-MB-231 human breast cancer cell proliferation. The combination of BA with Rh2 was also assessed. In MDA cells, combination treatment led to a decrease in the EC50 values of BA and Rh2 to 25.20 μM and 22.75 μM, respectively. In MCF-7 cells, the EC50 values of combined BA and Rh2 decreased to 27.68 μM and 25.41 μM, respectively. BA combined with Rh2 also improved the inhibition of MDA-MB-231 and MCF-7 cell migration and invasion compared to the individual compounds. Western blot analysis demonstrated upregulation in p-p53, p-p38, and p-ASK1 proteins while levels of TRAF2 were downregulated. These results suggest that BA combined with Rh2 exhibits synergistic effects against MDA-MB-231 and MCF-7 cell proliferation.

scholarly journals lncRNA NORAD Contributes to Colorectal Cancer Progression by Inhibition of miR-202-5p

2018 ◽  
Vol 26 (9) ◽  
pp. 1411-1418 ◽  
Author(s):  
Jie Zhang ◽  
Xiao-Yan Li ◽  
Ping Hu ◽  
Yuan-Sheng Ding
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Cellular Proliferation ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Competing Endogenous Rna

Previous study indicates that long noncoding RNA NORAD could serve as a competing endogenous RNA to pancreatic cancer metastasis. However, its role in colorectal cancer (CRC) needs to be investigated. In the present study, we found that the expression of NORAD was significantly upregulated in CRC tissues. Furthermore, the expression of NORAD was positively related with CRC metastasis and patients’ poor prognosis. Knockdown of NORAD markedly inhibited CRC cell proliferation, migration, and invasion but induced cell apoptosis in vitro. In vivo experiments also indicated an inhibitory effect of NORAD on tumor growth. Mechanistically, we found that NORAD served as a competing endogenous RNA for miR-202-5p. We found that there was an inverse relationship between the expression of NORAD and miR-202-5p in CRC tissues. Moreover, overexpression of miR-202-5p in SW480 and HCT116 cells significantly inhibited cellular proliferation, migration, and invasion. Taken together, our study demonstrated that the NORAD/miR-202-5p axis plays a pivotal function on CRC progression.

scholarly journals A comparison of the effects of kaempferol and quercetin on cytokine-induced pro-inflammatory status of cultured human endothelial cells

2008 ◽  
Vol 100 (5) ◽  
pp. 968-976 ◽  
Author(s):  
Irene Crespo ◽  
María V. García-Mediavilla ◽  
Belén Gutiérrez ◽  
Sonia Sánchez-Campos ◽  
María J. Tuñón ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Inhibitory Effect ◽  
Binding Activity ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Signalling Molecules ◽  
Inflammatory Status ◽  
Cox 2

We investigated the effects of the flavonols kaempferol and quercetin on the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), endothelial cell selectin (E-selectin), inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2), and on the activation of the signalling molecules NF-κB and activator protein-1 (AP-1), induced by a cytokine mixture in cultured human umbilical vein endothelial cells. Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 μmol/l but was significantly stronger for kaempferol at 5–50 μmol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10–50 μmol/l), ICAM-1 (50 μmol/l) and E-selectin (5–50 μmol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10–50 μmol/l), ICAM-1 (50 μmol/l) and E-selectin (50 μmol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5–50 μmol/l. The effect of kaempferol on NF-κB and AP-1 binding activity was weaker at high concentrations (50 μmol/l) as compared with quercetin. The present study indicates that differences exist in the modulation of pro-inflammatory genes and in the blockade of NF-κB and AP-1 by kaempferol and quercetin. The minor structural differences between both flavonols determine differences in their anti-inflammatory properties and in their efficiency in inhibiting signalling molecules.

Time and Dose Dependent Synergism Between Conventional Cytostatics and the p53-Modulating Small Molecule PRIMA-Meth in p53 Mutated Leukemic Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5029-5029
Author(s):  
Dina Ali ◽  
Christer Paul ◽  
S.ören Lehmann
Keyword(s):  
Synergistic Effect ◽  
Cell Survival ◽  
Synergistic Effects ◽  
Chemotherapeutic Agents ◽  
Stress Factors ◽  
Leukemic Cells ◽  
Chemotherapeutic Drugs ◽  
Cytostatic Drugs ◽  
Simultaneous Exposure ◽  
Survival Percentage

Abstract Background: P53 deletions and mutations can be found in 5 to 15% of patients with acute myeloid leukemia and in about 50% of all human cancers. Mutations in the p15 gene are associated with resistance to cancer chemotherapy. Furthermore, p53 is involved in the induction of apoptosis in response to many cellular stress factors. P53 mutations in AML are associated to poor prognosis and a decreased sensitivity to chemotherapeutic drugs. PRIMA-meth (APR-246) belongs to a new generation of the compounds proved to restore the function of p53. It has been shown that PRIMA-1 meth works synergistically with some cancer chemotherapeutic agents through mutant p53-dependent pathway. Aim: To identify a novel effective regimen for AML patients by incorporating PRIMA-meth. The study was performed in vitro in order to evaluate a regimen that can exert the most pronounced synergistic effect when combining PRIMA-meth with conventional chemotherapeutic drugs. Materials and Methods: After optimizing the doses of the drugs and the exposure time, cells were incubated with daunorubicin (0.01μM) cytarabine (0.5μM) and fludarabine (20μM) alone and in combination with PRIMA-meth (5, 10 and15μM). Three different timing schedules of the exposure were tested; one with 24 hours pretreatment with PRIMA-meth, one with 24 hours pretreatment with the cytostatic drugs and one with simultaneuous incubation of PRIMA-meth in combination with the cytostatics. After 96 hours of incubation, the cell viability was analyzed by a bioluminescence assay measuring ATP levels. Each experiment was done in triplicate. Results: Pre-incubation for 24 hours in PRIMA-meth exerted synergistic effects at 15μM in combination with all three tested drugs (table 1). This effect was superior to the combination effect seen when cells were pre-incubated with the cytostatic drugs where synergism was seen only with fludarabine. In the 24 hour pretreatment regimens, more potent synergism was found with fludarabine in combination with the higher PRIMA-meth concentrations (10μM and 15μM) irrespectively which drug was added first. Generally, the higher the prima-meth concentration, the better the response to combination therapy. With simultaneous exposure, synergism was found only with fludarabine in combination with PRIMA-meth at the highest concentration. N.B: Values represent ratio values between actual cell survival percentage and expected cell survival percentage (synergistic effect< or =0,8; additive effect >0,8<1,2). In conclusion, PRIMA-meth can exert synergistic effects in combination with conventional chemotherapeutic drugs in p53 mutated AML cells. Synergism could be seen with fludarabine irrespectively of the timing of the exposure whereas synergism with daunorubicin and cytarabine was seen only when preincubating cells with PRIMA-meth. Synergisms were seen when using PRIMA-meth at higher concentrations. This suggests that similar combinations are promising and should be used for combination treatments in clinical trials.

Synergistic Anticancer Effects between Curcumin and Doxorubicin in Drug Sensitive and Resistant Human Pediatric Leukemic Cell Lines.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4361-4361
Author(s):  
Cheppail Ramachandran ◽  
P.K. Raveendran Nair ◽  
Enrique Escalon ◽  
Steven J. Melnick ◽  
Ziad Khatib
Keyword(s):  
Synergistic Effect ◽  
Cell Lines ◽  
Combination Index ◽  
Synergistic Effects ◽  
Leukemic Cell ◽  
Inhibitory Effect ◽  
Leukemic Cell Lines ◽  
Combination Treatments ◽  
Anti Inflammatory

Abstract Curcumin (diferuloyl methane), the yellow colored chemopreventive agent from turmeric has anti-tumor, anti-inflammatory and anti-oxidant effects. The synergistic effect of curcumin and doxorubicin on cytotoxicity in leukemic cell lines was investigated preclinically in vitro for their eventual use in combination therapy in pediatric patients. Curcumin is cytotoxic to both sensitive (CEM) and resistant (CEM/VLB) cell lines with an IC50 value of 12 μM. Multi-drug resistant (MDR) cell line (CEM/VLB) showed 36.4-fold doxorubicin resistance based on DOX IC50 values of 0.14 μM and 5.1 μM for CEM and CEM/VLB cell lines. Analysis of cytotoxicity data by CalcuSyn program showed that curcumin and doxorubicin combination treatments are synergistic with combination index values less than 1 at IC50 (CEM=0.82; CEM/VLB =0.81) and IC75 (CEM=0.60; CEM/VLB=0.83) levels. Curcumin and doxorubicin induces G2/M arrest and apoptosis in tumor cells and the apoptosis data correlated with cytotoxicity values in both sensitive and resistant cell lines. The combination index values on the percentage of apoptosis induced by curcumin and doxorubicin combination treatments were less than 1 indicating the synergistic effect of both these agents on apoptosis. Doxorubicin treatment up regulated NF-κB activity in both CEM and CEM/VLB cell lines, although the level of up regulation is higher in CEM (2-fold) than CEM/VLB (1.5-fold) cell lines. Curcumin, on the other hand, is anti-inflammatory because of its significant inhibitory effect on NF-κB activity. Curcumin inhibited 80% and 50% of NF-κB activity in CEM and CEM/VLB cell lines in 24 h. These results showed that curcumin can be used either as a single or adjuvant agent along with doxorubicin because of the synergistic effects on apoptosis and cytotoxicity.

scholarly journals Antibodies against human neutrophil LECAM-1 (LAM-1/Leu-8/DREG-56 antigen) and endothelial cell ELAM-1 inhibit a common CD18-independent adhesion pathway in vitro

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 805-811 ◽  
Author(s):  
TK Kishimoto ◽  
RA Warnock ◽  
MA Jutila ◽  
EC Butcher ◽  
C Lane ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Neutrophil Function ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1

Neutrophil adhesion to interleukin-1 (IL-1)-stimulated human umbilical vein endothelial cells (HUVEC) involves the CD18 family of leukocyte integrins (lymphocyte function-associated antigen-1 [LFA-1], Mac-1, and p150,95) and LECAM-1 (DREG-56/LEU-8/LAM-1 antigen) on neutrophils and intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) on the endothelium. In this study, we compare CD18-independent adhesion pathways mediated by neutrophil LECAM- 1 and endothelial ELAM-1 and find that these two pathways overlap in a variety of assays: (1) anti-LECAM-1 and anti-ELAM-1 monoclonal antibody (MoAb) inhibit neutrophil binding to HUVEC, and the inhibitory effect is not additive; (2) anti-LECAM-1 MoAb, like anti-ELAM-1 MoAb, inhibits neutrophil binding to HUVEC stimulated for 3 hours with IL-1, but not to HUVEC stimulated for 8 hours, by which time ELAM-1 expression is downregulated; (3) anti-ELAM-1 MoAb has no effect on transendothelial migration, a CD18-dependent, LECAM-1-independent neutrophil function. Interestingly, anti-ELAM MoAb has a reduced but significant inhibitory effect on the adhesion of activated neutrophils that have shed their cell-surface LECAM-1. We also show that neutrophil binding to ELAM-1- transfected L cells is inhibited not only by anti-ELAM-1 but also by anti-LECAM-1 MoAb. These results suggest that LECAM-1 and ELAM-1 can operate in the same adhesion pathway, possibly as a receptor- counterreceptor pair. LECAM-1 and ELAM-1 are likely to interact with other ligands as well, perhaps through carbohydrate determinants that modify more than one glycoprotein.

MDM2 Antagonist Nutlin-3 Enhances Bortezomib-Mediated Mitochondrial Apoptosis In TP53-Mutated Mantle Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3920-3920
Author(s):  
Yoko Tabe ◽  
Linhua Jin ◽  
Kensuke Kojima ◽  
Yixin Zhou ◽  
Stefania Pittaluga ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cellular Proliferation ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Synergistic Effects ◽  
Single Agent ◽  
Flow Cytometric Analysis ◽  
B Cell Lymphoma ◽  
Chemotherapeutic Agents ◽  
Mantle Cell

Abstract Abstract 3920 Mantle cell lymphoma (MCL) is a subtype of B-cell lymphoma and frequently resistant to standard chemotherapeutic agents, and the aggressive blastoid MCL cases often possess mutant (mt-) TP53. Although a proteasome inhibitor bortezomib demonstrates single agent efficacy in MCL, more than 50% of the relapsed or refractory MCL are not enough sensitive to bortezomib. Therefore, development of rationally designed combinations of bortezomib and other antineoplastic agents is needed. We previously reported a dose- and time- dependent inhibition of cellular proliferation in wt-TP53 MCL cells by an MDM2 inhibitor nutlin-3, and its synergistic effects when combined with bortezomib in both mt-TP53- and wt-TP53- bearing MCL cells (Tabe et al., Clin Cancer Res. 2009). In this study, we investigated the molecular mechanism of the synergistical cytotoxic effects of nutlin-3/bortezomib in the mt-TP53 MCL cells which are intrinsically resistant to bortezomib. The MCL cell lines with wild-type and mutant TP53 (wt-TP53: Z-138, Granta-519, mt-TP53: MINO) have been utilized. First, we established the IC50 of nutlin-3 and bortezomib (nutlin-3: 19.1 μM for MINO, 8.2 μM for Granta 519, 1.0 μM for Z-138, bortezomib: 21.8 nM for MINO, 3.7 nM for Granta, 5.0 nM for Z138, MTS assay at 48 hours). The combination of nutlin-3 and bortezomib synergistically induced cytotoxicity more prominently in the bortezomib resistant and mt-TP53 bearing MINO cells (combination index: 0.05 for MINO, 0.71 for Granta 519, 0.12 for Z-138, Calcusyn software). The combination of nutlin-3/bortezomib caused G0/G1 cell cycle arrest in the bortezomib sensitive wt-TP53 Granta 519 and Z138, but not in MINO. In contrast, nutlin-3/bortezomib induced marked increase in the sub-G1 fraction in MINO, but only minimal or no further increase in Granta 519 and Z138, which was confirmed by annexin V/PI staining. BH3-only protein NOXA expression was increased by bortezomib in all tested cells, and the nutlin-3/bortezomib enhanced NOXA accumulation in MINO but not in Granta 519 and Z138 (western blot). On the other hand, anti-apoptotic Mcl-1 has been upregulated by bortezomib in Granta 519 and Z138. In MINO cells, Mcl-1 upregulation was induced only by nutlin-3/bortezomib, which was coimmunoprecipitated with NOXA along with the induction of caspase-3 and -9 cleavage products. We then, assess the subsequent conformational change of proapoptotic BAX/BAK by the nutlin-3/bortezmib combination in MINO (flow cytometric analysis). Taken together, our findings indicate that mitochondrial apoptotic pathway may be an important mechanism contributing to synergistic apoptosis induction by the nutlin-3/bortezomib combination in MCL cells expressing mt-TP53 and intrinsically resistant to bortezomib. The nutlin-3/bortezomib combination may be a potential efficient therapeutic strategy for the chemorefractory MCL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CBMT-46. MICRORNA-206 ATTENUATES GLIOMA CELL PROLIFERATION, MIGRATION, AND INVASION BY BLOCKING THE WNT/β-CATENIN PATHWAY VIA DIRECT TARGETING OF FRIZZLED 7

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi43-vi43
Author(s):  
Yingyi Wang ◽  
Fengqi Zhou ◽  
Chunsheng Zhao
Keyword(s):  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Three Dimensional ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Nude Mouse Model ◽  
Real Time Quantitative Pcr

Abstract Glioma is one of the most frequent primary malignant brain tumours in adults and accumulating evidence has shown that microRNAs (miRNAs) are associated with various types of tumours, including glioma. It is essential to acquire a better understanding of the roles and mechanisms of miRNAs in WNT-driven glioblastoma (GBM). Here, we report that miR-206 inhibited the WNT/β-catenin pathway by directly targeting Frizzled 7 (FZD7) and functioned as a tumour-suppressor in glioma. The expression of miR-206 in human samples and glioma cells was assessed by real-time quantitative PCR (RT-qPCR), fluorescence in situ hybridization (FISH), and histological analysis. Cell Counting Kit-8 (CCK-8), colony formation, EdU, flow cytometry, wound healing, transwell invasion, and three-dimensional migration were performed to observe cellular proliferation, migration, and invasion in vitro. The effects of miR-206 in vivo were investigated using a xenograft nude mouse model. miR-206 expression was significantly downregulated in glioma specimens. FZD7 was confirmed as a direct target of miR-206. GBM cell proliferation, migration, and invasion were blocked by restoring the expression of miR-206. Moreover, intracranial glioma models demonstrated an inhibitory effect of miR-206 on intracranial glioma tumour growth. Our results suggested that miR-206 plays a key role in blocking the WNT/β-catenin signalling pathway by suppressing FZD7 and provides a prospective therapeutic strategy for the treatment of malignant glioma and other WNT-driven tumours.

scholarly journals Synergistic Effects of Sulfated Polysaccharides from Mexican Seaweeds against Measles Virus

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Karla Morán-Santibañez ◽  
Lucia Elizabeth Cruz-Suárez ◽  
Denis Ricque-Marie ◽  
Daniel Robledo ◽  
Yolanda Freile-Pelegrín ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Measles Virus ◽  
Synergistic Effects ◽  
Antiviral Agents ◽  
Inhibitory Effect ◽  
Sulfated Polysaccharides ◽  
Eisenia Arborea ◽  
Pelvetia Compressa ◽  
Solieria Filiformis

Sulfated polysaccharides (SPs) extracted from five seaweed samples collected or cultivated in Mexico (Macrocystis pyrifera,Eisenia arborea,Pelvetia compressa,Ulva intestinalis, andSolieria filiformis) were tested in this study in order to evaluate their effect on measles virusin vitro. All polysaccharides showed antiviral activity (as measured by the reduction of syncytia formation) and low cytotoxicity (MTT assay) at inhibitory concentrations. SPs fromEisenia arboreaandSolieria filiformisshowed the highest antiviral activities (confirmed by qPCR) and were selected to determine their combined effect. Their synergistic effect was observed at low concentrations (0.0274 μg/mL and 0.011 μg/mL ofE. arboreaandS. filiformisSPs, resp.), which exhibited by far a higher inhibitory effect (96% syncytia reduction) in comparison to the individual SP effects (50% inhibition with 0.275 μg/mL and 0.985 μg/mL ofE. arboreaandS. filiformis, resp.). Time of addition experiments and viral penetration assays suggest that best activities of these SPs occur at different stages of infection. The synergistic effect would allow reducing the treatment dose and toxicity and minimizing or delaying the induction of antiviral resistance; sulfated polysaccharides of the tested seaweed species thus appear as promising candidates for the development of natural antiviral agents.

scholarly journals miR-371b-5p-Engineered Exosomes Enhances Tumor Inhibitory Effect

2021 ◽  
Vol 9 ◽  
Author(s):  
Qiang Xue ◽  
Yang Yang ◽  
Linlin Yang ◽  
Xiaodi Yan ◽  
Zihao Shen ◽  
...  
Keyword(s):  
Cell Viability ◽  
Tumor Cells ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Migration And Invasion ◽  
Drug Molecules ◽  
Tumor Tissues ◽  
Cellular Components

Background: Exosomes are well-known natural nanovesicles, that represent one of the recently discovered modes of intercellular communication due to their ability to transmit cellular components. Exosomes have been reported to have potential as natural vectors for carrying functional small RNAs and delivering chemotherapeutic agents to diseased cells. In this study, we aimed to investigate the role of exosomes in carrying miRNA for targeting tumor cells.Methods: We present a novel method for engineering exosomes with functional miR-317b-5b to target tumor cells. MiR-317b-5b exerts its anti-tumor function via its expression in tumors. RT-qPCR was performed to assess the levels of miR-371b-5p, FUT-4. Western blot was performed to measure the levels of CD9, CD81, and FUT-4 proteins. Confocal microscopy was used to observe the internalization of miR-317b-5b in tumor cells. CCK-8, EdU, flow cytometry, wound-healing migration and transwell assays were performed to evaluate cell viability, proliferation, migration, and invasion, respectively.Results: Our findings illustrated that miR-317b-5b-loaded engineered exosomes were internalized by tumor cells. MiR-317b-5b was overexpressed in tumor cells treated with miR-317b-5b-loaded engineered exosomes. The internalization of miR-317b-5b in tumor cells was accompanied by changes of cell viability, proliferation, apoptosis, and migratory and invasive capability. We found that miR-317b-5b-loaded engineered exosomes were presence in tumor tissue sections and miR-317b-5b was overexpressed in tumor tissues of osteosarcoma tumor-bearing mice infected with miR-317b-5b-loaded engineered exosomes. MiR-317b-5b-loaded engineered exosomes had the anti-tumor efficiency in vivo.Conclusion: Our findings show that miR-317b-5b-loaded engineered exosomes can be used as nanocarriers to deliver drug molecules such as miR-317b-5b both in vitro and in vivo to exert its anti-tumor functions.

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