scholarly journals The Effect of Triptolide-Loaded Exosomes on the Proliferation and Apoptosis of Human Ovarian Cancer SKOV3 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Huan Liu ◽  
Ming Shen ◽  
De Zhao ◽  
Dan Ru ◽  
Yourong Duan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Water Solubility ◽  
Tumor Growth Inhibition ◽  
Anticancer Efficacy ◽  
Skov3 Cells ◽  
Cell Proliferation Inhibition ◽  
Proliferation And Apoptosis

Triptolide has been proven to possess anticancer efficacy; however, its application in the clinical practice was limited by poor water solubility, hepatotoxicity, and nephrotoxicity. In this study, a triptolide-loaded exosomes delivery system (TP-Exos) was constructed and its effects on the proliferation and apoptosis of SKOV3 cells in vitro and in vivo were observed. SKOV3-exosomes (SK-Exos) were collected by ultracentrifugation and ultrafiltration centrifugation. TP-Exos was constructed by sonication and ultrafiltration centrifugation. SK-Exos and TP-Exos were characterized by transmission electron microscopy, western blotting, nanoparticle-tracking analysis, and high-performance liquid chromatography. Cellular uptake of exosomes, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, bromodeoxyuridine (BrdU) cell proliferation assay, and cell apoptosis experiment were used to study the effect of TP-Exos on ovarian cancer in vitro. Tumor-targeting study of exosomes, monitoring the tumor volume of mice, and TdT-mediated dUTP Nick-End labeling (TUNEL) assay were used to evaluate the effect of TP-Exos on ovarian cancer in vivo. The toxicity of TP-Exos in vivo was evaluated by liver and kidney function and histopathology of major organs (heart, liver, spleen, lung, kidney, and ovary). The results revealed that TP-Exos not only have the general characteristics of exosomes but also have high drug encapsulation efficiency. Besides, PKH26 labeled exosomes (PKH26-Exos) could be uptaken by SKOV3 cells, and Dir labeled exosomes (Dir-Exos) could be enriched to the tumor site of tumor bearing mice. Furthermore, the cytotoxic and apoptotic effects on SKOV3 cells of TP-Exos were weaker than those of free TP, and tumor cell proliferation inhibition and tumor growth inhibition were stronger than that of free TP. Moreover, TP-Exos have toxic effect on liver and spleen. In conclusion, the TP-Exos could be a promising strategy for ovarian cancer, but they need to be further optimized to attenuate the damage to liver and spleen.

scholarly journals NFATc1 regulates cell proliferation, migration, and invasion of ovarian cancer SKOV3 cells in vitro and in vivo

2016 ◽  
Vol 36 (2) ◽  
pp. 918-928 ◽  
Author(s):  
Long Li ◽  
Zhaoning Duan ◽  
Jihui Yu ◽  
Hong-Xing Dang
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Migration And Invasion ◽  
Skov3 Cells

scholarly journals Preparation nanoparticles of β-cyclodextrin loaded Scutellarein anti-tumor activity research by targeting integrin αvβ3

2021 ◽  
Author(s):  
JUNDONG WANG ◽  
TIANHAO LI ◽  
CHAOCHI YUE ◽  
SEN ZHONG ◽  
XIANGDONG YANG ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Water Solubility ◽  
Integrin Αvβ3 ◽  
Human Colon ◽  
In Vivo Studies ◽  
Human Colon Cancer ◽  
Proliferation And Apoptosis

Abstract BackgroundThe problems associated with poor water solubility of anticancer drugs are one of the most important challenges in achieving effective cancer therapy. The present study was designed to evaluate the effect of Scutellarein on human colon cancer cells in vitro by using a target αvβ-3 novel Scutellarein (Scu)-loaded niosome nanoparticle (β-CD-CL-Scu-cRGD).Resultsβ-CD-CL-Scu-cRGD has a diameter of 140.2nm and a zeta potential of -11.3 mV with a constant physicochemical stability. The MTT assay showed both Scu and β-CD-CL-Scu-cRGD caused a decrease in cell proliferation and viability of HT29, but β-CD-CL-Scu-cRGD showed better activity in vitro. Colony formation assay and flow cytometry assay showed that β-CD-CL-Scu-cRGD has a better effect on cell proliferation and apoptosis.ConclusionsAlthough further in vivo studies are necessary, our results suggested that β-CD-CL-Scu-cRGD could be an outstanding carrier to deliver Scu for potential therapeutic approaches into colon cancer.

scholarly journals Long non-coding RNA PTPRG-AS1 promotes cell tumorigenicity in epithelial ovarian cancer by decoying microRNA-545-3p and consequently enhancing HDAC4 expression

2020 ◽  
Author(s):  
Juanjuan Shi ◽  
Xijian Xu ◽  
Dan Zhang ◽  
Jiuyan Zhang ◽  
Hui Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background: Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also performed to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC.Methods: Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays.Results: Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro, and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. Regarding the mechanism, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4.Conclusions: PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

scholarly journals STK3 Suppresses Ovarian Cancer Progression by Activating NF-κB Signaling to Recruit CD8+ T-Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Xiangyu Wang ◽  
Fengmian Wang ◽  
Zhi-Gang Zhang ◽  
Xiao-Mei Yang ◽  
Rong Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
T Cells ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Gene Set Enrichment Analysis ◽  
Ovarian Cancer Cells ◽  
And Migration

Serine/threonine protein kinase-3 (STK3) is a critical molecule of the Hippo pathway but little is known about its biological functions in the ovarian cancer development. We demonstrated the roles of STK3 in ovarian cancer. Existing databases were used to study the expression profile of STK3. STK3 was significantly downregulated in OC patients, and the low STK3 expression was correlated with a poor prognosis. In vitro cell proliferation, apoptosis, and migration assays, and in vivo subcutaneous xenograft tumor models were used to determine the roles of STK3. The overexpression of STK3 significantly inhibited cell proliferation, apoptosis, and migration of ovarian cancer cells in vitro and tumor growth in vivo. Bisulfite sequencing PCR analysis was performed to validate the methylation of STK3 in ovarian cancer. RNA sequencing and gene set enrichment analysis (GSEA) were used to compare the transcriptome changes in the STK3 overexpression ovarian cancer and control cells. The signaling pathway was analyzed by western blotting. STK3 promoted the migration of CD8+ T-cells by activating nuclear transcription factor κB (NF-κB) signaling. STK3 is a potential predictor of OC. It plays an important role in suppressing tumor growth of ovarian cancer and in chemotaxis of CD8+ T-cells.

TRIAP1 Inhibition Activates the Cytochrome c/Apaf-1/Caspase-9 Signaling Pathway to Enhance Human Ovarian Cancer Sensitivity to Cisplatin

Chemotherapy ◽  
2019 ◽  
Vol 64 (3) ◽  
pp. 119-128 ◽  
Author(s):  
Tian-Mei Zhang
Keyword(s):  
Ovarian Cancer ◽  
Nude Mice ◽  
Cell Apoptosis ◽  
Caspase 9 ◽  
Ovarian Carcinoma Cell Line ◽  
Skov3 Cells ◽  
Cyt C ◽  
Sirna Group

Objective: To investigate whether TRIAP1inhibition affects the ovarian cancer cell resistance to cisplatin (DDP) via the Cyt c/Apaf-1/caspase-9 pathway by in vitro and in vivo experiments. Methods: CCK8 assay was performed to find out how treatment with both TRIAP1 siRNA and DDP affects the cell viability of SKOV3 cells and DDP-resistant human ovarian carcinoma cell line SKOV3/DDP. SKOV3/DDP cells were transfected with control siRNA or TRIAP1 siRNA before 24 h of treatment with DDP (5 μg/mL). Flow cytometry was employed to detect cell apoptosis and Western blot to examine the expressions of Cyt c/Apaf-1/caspase-9 pathway-related proteins. SKOV3/DDP cells transfected with control siRNA or TRIAP1 siRNA were subcutaneously injected into BALB/c-nu/nu nude mice followed by the intraperitoneal injection of DDP (4 mg/kg). Cyt c/Apaf-1/caspase-9 pathway in transplanted tumors was detected by immunohistochemistry. Results: TRIAP1 expression declined in SKOV3 cells when compared with SKOV3/DDP cells. The proliferation rate was lower in SKOV3/DDP cells transfected with TRIAP1 siRNA combined with treatment of DDP (1, 2, 4, 6, 8, 16, 32 μg/mL) than in those transfected with control siRNA. Moreover, the TRIAP1 siRNA group had an increased SKOV3/DDP cell apoptosis rate with the activation of the Cyt c/Apaf-1/caspase-9 pathway. During DDP treatment, nude mice in TRIAP1 siRNA group had slower growth and smaller size of transplanted tumor than those in control siRNA group, with increased expression of Cyt c, Apaf-1, and caspase-9. Conclusion: TRIAP1 inhibition may enhance the sensitivity of SKOV3/DDP cells to cisplatin via activation of the Cyt c/Apaf-1/caspase-9 pathway.

scholarly journals Development of Novel Silyl Cyanocinnamic Acid Derivatives as Metabolic Plasticity Inhibitors for Cancer Treatment

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Grady L. Nelson ◽  
Conor T. Ronayne ◽  
Lucas N. Solano ◽  
Sravan K. Jonnalagadda ◽  
Shirisha Jonnalagadda ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Anticancer Agents ◽  
Single Agent ◽  
Monocarboxylate Transporter ◽  
Tumor Xenograft ◽  
Anticancer Efficacy ◽  
Cell Proliferation Inhibition ◽  
Cyanocinnamic Acid

AbstractNovel silyl cyanocinnamic acid derivatives have been synthesized and evaluated as potential anticancer agents. In vitro studies reveal that lead derivatives 2a and 2b have enhanced cancer cell proliferation inhibition properties when compared to the parent monocarboxylate transporter (MCT) inhibitor cyano-hydroxycinnamic acid (CHC). Further, candidate compounds exhibit several-fold more potent MCT1 inhibition properties as determined by lactate-uptake studies, and these studies are supported by MCT homology modeling and computational inhibitor-docking studies. In vitro effects on glycolysis and mitochondrial metabolism also illustrate that the lead derivatives 2a and 2b lead to significant effects on both metabolic pathways. In vivo systemic toxicity and efficacy studies in colorectal cancer cell WiDr tumor xenograft demonstrate that candidate compounds are well tolerated and exhibit good single agent anticancer efficacy properties.

scholarly journals Cordyceps militaris Exerts Antitumor Effect on Carboplatin-Resistant Ovarian Cancer via Activation of ATF3/TP53 Signaling In Vitro and In Vivo

2020 ◽  
Vol 15 (1) ◽  
pp. 1934578X2090255
Author(s):  
Eunbi Jo ◽  
Hyun-Jin Jang ◽  
Kyeong E. Yang ◽  
Min S. Jang ◽  
Yang H. Huh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
B Cell Lymphoma ◽  
Cordyceps Militaris ◽  
Exponential Growth Phase ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Parp 1

This study aimed to investigate the effect of Cordyceps militaris extract on the proliferation and apoptosis of carboplatin- resistant SKOV-3 and determine the underlying mechanisms for overcoming carboplatin resistance in human ovarian cancer. We cultured the carboplatin-resistant SKOV-3 cells in vitro until the exponential growth phase and then treated with different concentrations of C. militaris for 24, 48, and 72 hours. We performed cell proliferation assay, cell morphological change assessment using transmission electron microscopy, apoptosis assay, and immunoblotting to measure the protein expression of caspase-3 and -8, poly (ADP-ribose) polymerase (PARP)-1, B-cell lymphoma (Bcl)-2, and activating transcription factor 3 (ATF3)/TP53 signaling-related proteins. As a result, C. militaris reduced the viability of carboplatin-resistant SKOV-3 and induced morphological disruptions in a dose- and time-dependent manner. The gene expression profiles indicated a reprogramming pattern of the previously known and unknown genes and transcription factors associated with the action of TCTN3 on carboplatin-resistant SKOV-3 cells. We also confirmed the C. militaris-induced activation of the ATF3/TP53 pathway. Immunoblotting indicated that cotreatment of C. militaris and carboplatin-mediated ATF3/TP53 upregulation induced apoptosis in the carboplatin-resistant SKOV-3 cells, which are involved in the serial activation of pro-apoptotic proteins, including Bcl-2, Bax, caspases, and PARP-1. Further, when the ATF3 and TP53 expression increased, the CHOP and PUMA expressions were upregulated. Consequently, the upregulated CHOP/PUMA expression activated the positive regulation of the apoptotic signaling pathway. In addition, it decreased the Bcl-2 expression, leading to marked ovarian cancer cells sensitive to carboplatin by enhancing apoptosis. We then corroborated these results using in vivo experiments. Taken together, C. militaris inhibits carboplatin-resistant SKOV-3 cell proliferation and induces apoptosis possibly through ATF3/TP53 signaling upregulation and CHOP/PUMA activation. Therefore, our findings provide new insights into the treatment of carboplatin-resistant ovarian cancer using C. militaris.

scholarly journals PTP4A3, A Novel Target Gene of HIF-1alpha, Participates in Benzene-Induced Cell Proliferation Inhibition and Apoptosis through PI3K/AKT Pathway

2020 ◽  
Vol 17 (3) ◽  
pp. 910
Author(s):  
Yunqiu Pu ◽  
Fengxia Sun ◽  
Rongli Sun ◽  
Zhaodi Man ◽  
Shuangbin Ji ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Target Gene ◽  
Akt Pathway ◽  
Proliferation Inhibition ◽  
Cell Proliferation Inhibition ◽  
A Cell ◽  
Novel Target ◽  
In Cells

Benzene, a commonly used chemical, has been confirmed to specifically affect the hematopoietic system as well as overall human health. PTP4A3 is overexpressed in leukemia cells and is related to cell proliferation. We previously found that HIF-1alpha was involved in benzene toxicity and PTP4A3 may be the target gene of HIF-1alpha via ChIP-seq. The aim of this study is to confirm the relationship between HIF-1alpha and PTP4A3 in benzene toxicity, as well as the function of PTP4A3 on cell toxicity induced by 1,4-benzoquinone (1,4-BQ). Our results indicate that HIF-1alpha could regulate PTP4A3 with in vivo and in vitro experiments. A cell line with suppressed PTP4A3 was established to investigate the function of PTP4A3 in 1,4-BQ toxicity in vitro. The results revealed that cell proliferation inhibition was more aggravated in PTP4A3 low-expression cells than in the control cells after 1,4-BQ treatment. The relative oxygen species (ROS) significantly increased in cells with inhibited PTP4A3, while the rise was inferior to the control cells at the 20 μM 1,4-BQ group. An increase in DNA damage was seen in PTP4A3 down-regulated cells at the 10 μM 1,4-BQ group, whereas the results reversed at the concentration of 20 μM. Moreover, the apoptosis rate increased higher in down-regulated PTP4A3 cells after 1,4-BQ exposure. In addition, PI3K/AKT pathway was significantly restrained in cells with inhibited PTP4A3 after 1,4-BQ treatment. Our results indicate that HIF-1alpha may regulate PTP4A3 to be involved in benzene toxicity. Inhibition of PTP4A3 could aggravate cell proliferation suppression and apoptosis by regulating PI3K/AKT pathway after 1,4-BQ treatment.

scholarly journals Human Bone Marrow-Derived Mesenchymal Stem Cell-Secreted Exosomes Overexpressing Microrna-124-3p Inhibit DLBCL Progression By Downregulating  NFATc1

2020 ◽  
Author(s):  
Xiaolei Ding ◽  
Lingzhi Xu ◽  
Xiuhua Sun ◽  
Xiaoxuan Zhao ◽  
Bing Gao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
B Cell Lymphoma ◽  
Inhibitory Effect ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Proliferation And Apoptosis ◽  
Microrna 124

Abstract Background: Exosomes play important roles in intercellular communication by delivering microRNAs (miRNAs) that mediate tumor initiation and development, including those in diffuse large B cell lymphoma (DLBCL). To date, however, limited studies on the inhibitory effect of exosomes derived from human bone marrow-derived mesenchymal stem cells (hBMSCs) on DLBCL progression have been reported. Therefore, this study aimed to investigate the role of hBMSC-secreted exosomes carrying microRNA-124-3p in the development of DLBCL.Methods: Microarray-based expression analysis was adopted to identify differentially expressed genes and regulatory miRNAs, which revealed the candidate NFATc1. Next, the binding affinity between miR-124-3p and NFATc1 was using luciferase activity assays. The mechanism underlying NFATc1 regulation was investigated using lentiviral transfections. Subsequently, DLBCL cells were cocultured with exosomes derived from hBMSCs transfected with a miR-124-3p mimic or control. Proliferation and apoptosis were measured in vitro. Finally, the effects of hBMSC-derived miR-124-3p on tumor growth were investigated in vivo.Results: MiR-124-3p was downregulated while NFATc1 was upregulated in DLBCL cells. MiR-124-3p specifically targeted and negatively regulated the expression of NFATc1 in DLBCL cells, upregulated miR-124-3p-inhibited DLBCL cell proliferation and promoted apoptosis. In addition, we found that hBMSC-derived exosomes carrying miR-124-3p repressed DLBCL cell proliferation both in vitro and in vivo.Conclusion: hBMSC-derived exosomal miR-124-3p represses the development of DLBCL through the downregulation of NFATc1.

scholarly journals Lamin B2 promotes the progression of triple negative breast cancer via mediating cell proliferation and apoptosis

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Cui-Cui Zhao ◽  
Jing Chen ◽  
Li-Ying Zhang ◽  
Hong Liu ◽  
Chuan-Gui Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
The Cancer Genome Atlas ◽  
Proliferation And Apoptosis

Abstract Triple negative breast cancer (TNBC) is a more common type of breast cancer with high distant metastasis and poor prognosis. The potential role of lamins in cancer progression has been widely revealed. However, the function of lamin B2 (LMNB2) in TNBC progression is still unclear. The present study aimed to investigate the role of LMNB2 in TNBC. The cancer genome atlas (TCGA) database analysis and immunohistochemistry (IHC) were performed to examine LMNB2 expression levels. LMNB2 short hairpin RNA plasmid or lentivirus was used to deplete the expression of LMNB2 in human TNBC cell lines including MDA-MB-468 and MDA-MB-231. Alterations in cell proliferation and apoptosis in vitro and the nude mouse tumorigenicity assay in vivo were subsequently analyzed. The human TNBC tissues shown high expression of LMNB2 according to the bioinformation analysis and IHC assays. LMNB2 expression was correlated with the clinical pathological features of TNBC patients, including pTNM stage and lymph node metastasis. Through in vitro and in vivo assays, we confirmed LMNB2 depletion suppressed the proliferation and induced the apoptosis of TNBC cells, and inhibited tumor growth of TNBC cells in mice, with the decrease in Ki67 expression or the increase in caspase-3 expression. In conclusion, LMNB2 may promote TNBC progression and could serve as a potential therapeutic target for TNBC treatment.

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