Preparation of Magnetic Drug Loaded Nanoparticles and Its Anticancer Efficacy Against Nasopharyngeal Carcinoma Cells

2021 ◽  
Vol 13 (5) ◽  
pp. 857-863
Author(s):  
Jingjing Chen ◽  
Cheng Kang
Keyword(s):  
Magnetic Nanoparticles ◽  
Nasopharyngeal Carcinoma ◽  
Therapeutic Effect ◽  
Inhibitory Effect ◽  
Antagonistic Effect ◽  
Anticancer Efficacy ◽  
Normal Tissues ◽  
Chemotherapy Agent

As an important drug for the treatment of cancer, cis-diamine dichloroplatinum (CDDP) has poor solubility and antagonistic effect when it is used as a chemotherapy agent alone, leading to the insufficient dose in actual administration. In order to solve the above problems, increase the targeting property of CDDP carrier and prolong the half-life period of CDDP’s sustained-release, it is necessary to design a magnetic nano-carrier for CDDP with magnetic targeting function to reduce the damage of CDDP to normal tissues in vivo and improve the therapeutic effect of cancer. Carboxymethyl chitosan (CMCS) is used to directly coat oleic acid (OA)-modified Fe3O4 nanoparticles (OA-Fe3O4 NPs) to create the nano-scale CMCS magnetic nanoparticles (CMCS/OA-Fe2O3 NPs), and CDDP loaded magnetic nanoparticles (CMCS/OA-Fe2O3 NPs/CDDP) are prepared by the bonding interaction between carboxyl groups on the surface of CMCS and the anticancer drug CDDP. The magnetic drug loaded nanoparticles are characterized, and the results show that the magnetic nanoparticles are successfully embedded in CMCS and loaded with CDDP, with the drug load of 43.65 ± 2.37%. MTT assay, flow cytometry and invasion assay are applied to evaluate the inhibitory effect of magnetic drug loaded nanoparticles to nasopharyngeal carcinoma (NPC) cells HNE-1. The results suggest that the magnetic drug loaded nanoparticles successfully prepared have significant inhibitory effect on HNE-1 cells in vitro. Therefore, the magnetic drug loaded nanoparticles prepared have a good therapeutic effect on NPC.

scholarly journals MTA1-Dependent Anticancer Activity of Gnetin C in Prostate Cancer

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2096 ◽  
Author(s):  
Avinash Kumar ◽  
Kshiti Dholakia ◽  
Gabriela Sikorska ◽  
Luis A. Martinez ◽  
Anait S. Levenson
Keyword(s):  
Prostate Cancer ◽  
Intraepithelial Neoplasia ◽  
Inhibitory Effect ◽  
Tumor Aggressiveness ◽  
Therapeutic Approaches ◽  
Anticancer Efficacy ◽  
Anticancer Effects ◽  
And Migration

The overexpression of metastasis-associated protein 1 (MTA1) in prostate cancer (PCa) contributes to tumor aggressiveness and metastasis. We have reported the inhibition of MTA1 by resveratrol and its potent analog pterostilbene in vitro and in vivo. We have demonstrated that pterostilbene treatment blocks the progression of prostatic intraepithelial neoplasia and adenocarcinoma in mouse models by inhibiting MTA1 expression and signaling. In the current study, we investigated the MTA1 targeted anticancer effects of Gnetin C, a resveratrol dimer, in comparison with resveratrol and pterostilbene. Using DU145 and PC3M PCa cells, we found that Gnetin C downregulates MTA1 more potently than resveratrol and pterostilbene. Further, Gnetin C demonstrated significant MTA1-mediated inhibitory effect on cell viability, colony formation, and migration, while showing a more potent induction of cell death than resveratrol or pterostilbene. In addition, we identified Gnetin C-induced substantial ETS2 (erythroblastosis E26 transformation-specific 2) downregulation, which is not only MTA1-dependent, but is also independent of MTA1 as a possible mechanism for the superior anticancer efficacy of Gnetin C in PCa. Together, these findings underscore the importance of novel potent resveratrol dimer, Gnetin C, as a clinically promising agent for the future development of chemopreventive and possibly combinatorial therapeutic approaches in PCa.

scholarly journals Cephalosporin Antibiotics Specifically Enhance Conventional Chemotherapy in Nasopharyngeal Cancer

2020 ◽  
Author(s):  
Xiao-Qiong He ◽  
Qian Yao ◽  
Zhong Yu Song ◽  
Dan Fan ◽  
Yu Tong You ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cancer Cells ◽  
Nasopharyngeal Cancer ◽  
Combination Group ◽  
Conventional Chemotherapy ◽  
Microarray Gene Expression ◽  
Anticancer Efficacy ◽  
Cephalosporin Antibiotics

Abstract Background: Cephalosporin antibiotics can drastically upregulate the expression of HMOX1 in nasopharyngeal carcinoma cells. HMOX1 has dual role in cancer cells, and is involved in chemoresistance. Cephalosporin antibiotics are widely used in the treatment of bacteria infectious diseases in cancer patients. Whether they affect the efficacy of chemotherapy is unknown. Methods: Comparisons between cefotaxime and the combination of cefotaxime and cisplatin were carried out throughout the study. Cell viability was detected by MTT method. Influence on clone formation of cancer cells was investigated by plate clone formation assay. The in vivo anticancer effect was determined via cancer xenograft in mice. Flow cytometry analysis was used to detect the apoptosis. Microarray gene expression profiling was analyzed using Gene Ontology analysis, and the differential genes were validated by RT-qPCR. Results: Cefotaxime specifically, selectively and synergistically enhanced the anticancer efficacy of cisplatin in nasopharyngeal carcinoma both in vitro and in vivo without increasing the toxicity, but it inhibited the cytotoxic effects of cisplatin in other cancers. Combination of cefotaxime and cisplatin significantly regulated 5 genes in direction favoring the enhancement of anticancer efficacy; of which, THBS1 and LAPTM5 were upregulated; PPP3CB, STAG1 and NCOA5 were downregulated jointly. HMOX1 contributes to the anticancer efficacy in combination group. Upregulated genes significantly modulated 18 apoptotic pathways, downregulated genes mainly affected assembly of genetic materials. Conclusion: Cephalosporin antibiotics are excellent and safe sensitizers of conventional chemotherapy in the treatment of nasopharyngeal carcinoma, but should be carefully used in other cancers.

LncRNA DUXAP8 promotes the progression of laryngeal cancer through targeting miR-384/ POU2F1 axis

2020 ◽  
Author(s):  
Zhanfeng Yan ◽  
Xiaohui Wen ◽  
Jinsheng Dai ◽  
Jinfeng Liu ◽  
Pengpeng Hao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Laryngeal Cancer ◽  
Tumor Model ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
High Level

Abstract Background Laryngeal cancer is the highest incidence of head and neck cancers in the world. Increasing evidences have demonstrated that long non-coding RNAs (lncRNAs) play crucial roles in the progression of laryngeal cancer. Despite of the essential role of lncRNA DUXAP8 in many human cancers, its function and specific mechanisms in laryngeal cancer are poorly understood. Methods Differentially expression analysis of lncRNAs in GSE59652 dataset was performed by using limma package of R language. The expression of DUXAP8, miR-384 and candidate mRNAs was evaluated by qRT-PCR. Luciferase reporter assay and RIP assay were performed to determine the direct correlation between DUXAP8, miR-384 and POU2F1. Cell proliferation of laryngeal cancer cell lines TU212 and TU177 cells was evaluated by using CCK-8 assay, colony formation assay and EdU staining assay. Xenograft tumor model in vivo and rescue experiments were performed to explore the function and mechanisms of DUXAP8 in laryngeal cancer. Results The expression of DUXAP8 in tumor tissues was higher than that in adjacent normal tissues. High level of DUXAP8 was closely correlated to the worse prognosis of laryngeal cancer patients. Knockdown of DUXAP8 inhibited the proliferation of TU212 and TU177 cells in vitro, as well as tumor growth in vivo. Furthermore, overexpression of POU2F1 significantly attenuated the inhibitory effect of sh-DUXAP8 on cell proliferation of TU212 and TU177 cells. In addition, sh-DUXAP8 significantly decreased the expression of DUXAP8 and POU2F1, while increased miR-384 expression in tumor tissues compared with sh-NC group. Conclusion DUXAP8 acted as a sponge of tumor suppressor miR-384 and then upregulated POU2F1 expression, thereby promoted the development of laryngeal cancer. Our findings suggest that DUXAP8 may serve as a potential therapeutic target for laryngeal cancer.

3,3′,5′-Triiodothyronine inhibits ontogenetic development of iodothyronine-5′-deiodinase in the liver of the neonatal mouse

1988 ◽  
Vol 119 (2) ◽  
pp. 181-188 ◽  
Author(s):  
Doo Chol Han ◽  
Kanji Sato ◽  
Yuko Fujii ◽  
Minoru Ozawa ◽  
Hidehito Imamura ◽  
...  
Keyword(s):  
Single Injection ◽  
Inhibitory Effect ◽  
Antagonistic Effect ◽  
Time Dependent ◽  
Dependent Manner ◽  
Neonatal Mice ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Abstract. To elucidate the effect of rT3 on iodothyronine-5′-deiodinating activity (I-5′-DA) in the liver of neonatal mice, rT3 was injected sc on the 5–8th day after birth and I-5′-DA in the liver was determined. A single injection of rT3 (0.01–1 μg/g) inhibited the ontogenetically developing I-5′-DA in a dose- and time-dependent manner. The inhibitory effect was reversible and specific for I-5′-DA. Lineweaver-Burk analysis revealed that the time- and dose-dependent decrease in the enzyme activity was due to a decrease in Vmax with no alteration in Km values (5 × 10−8 mol/l). The maximal inhibitory effect was observed at a dose of 1 μg rT3/g, whereas the inhibitory effect was diminished at greater doses (4–10 μg/g), probably owing to a contamination with T4 of the rT3 preparation administered. Furthermore, consistent with our previous in vitro findings, rT3 inhibited the I-5′-DA induced by T3 in the liver of neonatal mice. These findings suggest that rT3 inhibited I-5′-DA in the liver of neonatal mice by decreasing the amount of enzyme available to the substrate and that rT3 also elicited an antagonistic effect against T3 in the induction of I-5′-DA in vivo.

scholarly journals Therapeutic Evaluation of Palbociclib and Its Compatibility with Other Chemotherapies in Primary and Recurrent Nasopharyngeal Carcinoma

2020 ◽  
Author(s):  
Zhichao Xue ◽  
Vivian Wai Yan Lui ◽  
Yongshu Li ◽  
Jia Lin ◽  
Chanping You ◽  
...  
Keyword(s):  
Cell Death ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Therapeutic Option ◽  
Substantial Reduction ◽  
Inhibitory Effect ◽  
High Dose ◽  
Ki 67

Abstract Background: Recent genomic analyses revealed that druggable molecule targets could only be detected in around 6% of nasopharyngeal carcinoma (NPC) patients. Yet, an addiction to dysregulated CDK4/6-cyclinD1 signalling pathway is an essential event in the pathogenesis of NPC. Using our newly established xenografts and cell lines derived from primary, recurrent and metastatic NPC, we aimed to evaluate the therapeutic efficacy of a specific CDK4/6 inhibitor, palbociclib, and its compatibility with other chemodrugs in treating NPC.Methods: The efficacy of single treatment of palbociclib on NPC models was first evaluated, followed by concurrent treatment with cisplatin or suberanilohydroxamic acid (SAHA). RNA sequencing was used to profile the related pathways in governing the drug response. Palbociclib-resistant NPC cell lines were also established to demonstrate if cisplatin could be used as a second-line treatment once the cells developed resistance to palbociclib. The efficacy of palbociclib treatment on cisplatin-resistant NPC cells was also examined. Results: Palbociclib single drug treatment was confirmed to have a cell cycle arresting effect of NPC cells in G1 phase in vitro. It also had a significant inhibitory effect in all the 6 NPC tumor models in vivo, with a substantial reduction in total tumor volume and proliferation marker Ki-67. Concurrent use of palbociclib dampened the cytotoxic effect of cisplatin in NPC cells in vitro. Notably, combination of palbociclib with SAHA resulted in synergistic cell death of NPC both in vitro and in vivo. Autophagy-associated cell death was found to be involved in the enhanced tumor growth inhibitory effect in the combined palbociclib+SAHA treatment. NPC cell lines trained to sustain growth in high dose of palbociclib and cisplatin remained sensitive in subsequent treatment of cisplatin or palbociclib respectively.Conclusions: This study provides essential evidences to position palbociclib as an alternative therapeutic option to NPC treatment, and to aware the effective administrative timing of palbociclib with other chemodrugs. The findings give the basis for planning of the first-in-human clinical trials of palbociclib regimens in NPC patients.

scholarly journals Re-Evaluation of Combinational Efficacy and Synergy of the Italian Protocol In Vitro: Are We Truly Optimizing Benefit or Permitting Unwanted Toxicity?

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1190
Author(s):  
Chitra Subramanian ◽  
Reid McCallister ◽  
Dawn Kuszynski ◽  
Mark S. Cohen
Keyword(s):  
Synergistic Effect ◽  
Cell Lines ◽  
Synergistic Effects ◽  
Antagonistic Effect ◽  
Steroidogenic Enzymes ◽  
In Vivo Evaluation ◽  
Anticancer Efficacy ◽  
Lower Toxicity

Introduction: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, with very poor prognosis as a majority of the patients have advanced disease at the time of diagnosis. Currently, adjuvant therapy for most patients consists of either mitotane (M) alone or in combination with multi-drug chemotherapeutics such as etoposide (E), doxorubicin (D), and cisplatin (P), known as the Italian protocol (IP; EDPM). This multi-drug treatment regimen, however, carries significant toxicity potential for patients. One way to improve toxicity profiles with these drugs in combination is to understand where their synergy occurs and over what dosing range so that lower dose regimens could be applied in combination with equal or improved efficacy. We hypothesize that a better understanding of the synergistic effects as well as the regulation of steroidogenic enzymes during combination therapy may provide more optimized combinational options with good potency and lower toxicity profiles. Methods: Two human ACC cell lines, NCI-H295R (hormonally active) and SW13 (hormonally inactive), were grown in 2D culture in appropriate growth medium. The viability of the cells after treatment with varying concentrations of the drugs (E, D, and P) either alone or in combinations with M was determined using the CellTiter Glow assay after 72 h, and the combination index for each was calculated using Compusyn by the Chou–Talalay method. The expression levels of enzymes associated with steroidogenesis were evaluated by RT-PCR in NCI-H295R. Results: When both cell lines were treated with M (ranging 25–50 μM), +E (ranging 18.75–75 μM), and +D (ranging 0.625–2.5 μM) we observed a synergistic effect (CI < 1) with potency equivalent to the full Italian protocol (IP), whereas combining M + P + D had an antagonistic effect (CI > 1) indicating the negative effect of adding cisplatin in the combination. Comparing the hormonally active and inactive cell lines, M + P + E was antagonistic in NCI-H295R and synergistic in SW13. Treatment of NCI-H295R cells with antagonistic combinations (M + P + D, M + P + E) resulted in a significant decrease in the levels of steroidogenic enzymes STAR, CYP11A1, and CYP21A2 compared to IP (p < 0.05) while M + E + D resulted in increased expression or no significant effect compared to IP across all genes tested. Conclusions: The synergistic effect for M + E + D was significant and equivalent in potency to the full IP in both cell lines and resulted in a steroidogenic gene expression profile similar to or better than that of full IP, warranting further evaluation. Future in vivo evaluation of the combination of M + E + D (with removal of P from the IP regimen) may lower toxicity while maintaining anticancer efficacy in ACC.

scholarly journals Gentiana macrophylla exhibits a potential therapeutic effect on osteoarthritis (OA) via modulating disease-related proteins

2021 ◽  
Author(s):  
Haitao Xu ◽  
Ningyang Gao ◽  
Yuxin Zheng
Keyword(s):  
Therapeutic Effect ◽  
Dose Group ◽  
Inhibitory Effect ◽  
High Dose ◽  
In Vivo Models ◽  
Regulated Expression ◽  
Group A ◽  
Gentiana Macrophylla

IntroductionProstaglandin E2 (PGE2) has been reported to cause cartilage degradation in the pathogenesis of osteoarthritis (OA). Matrix metallopeptidases (MMPs) play important roles in the pathogenesis of OA, while p-AKT and p-P39 signaling pathways were reported to be activated in the pathogenesis of OA. In this study, we aimed to investigate the effect of Gentiana macrophylla (GM) on the treatment of OA.Material and methodsPrimary rat chondrocytes were treated with PBS, IL-1β, and IL-1β+GM respectively to established in vitro models, and in vivo models were set up as a SHAM group, a monoiodoacetic acid (MIA) group, a MIA+GM (low dose) group and a MIA+GM (high dose) group.ResultsIn primary rat chondrocytes, the IL-1β treatment elevated the expression of PGE2 and COX2 mRNA. However, the GM treatment reduced the expression of PGE2 mRNA and COX2 mRNA. Also, the GM treatment reduced the expression of above MMPs in primary rat chondrocytes treated with IL-1β. Moreover, unlike P38 and AKT, GM treatment could reduce the expression of p-P38 and p-AKT in primary rat chondrocytes treated with IL-1β. Also, GM treatment reduced the up-regulated expression of COX2, MMPs including MMP-1, MMP-3 and MMP-13, and p-P38 and p-AKT in OA rat models, thus exhibiting a therapeutic effect on OA pathology.ConclusionsOur study demonstrated the inhibitory effect of GM on the up-regulated expression of PGE2, Cyclooxygenase-2 (COX-2), MMPs including MMP-1, MMP-3 and MMP-13, AKT and P38 in OA models, thus verifying the therapeutic effect of GM on the treatment of OA.

scholarly journals Therapeutic effect of YSY01 on osteoarthritis in rabbit: involvement of suppressing signaling pathway of NF-kB and MMP-9

2021 ◽  
Author(s):  
Zhou Yang ◽  
Feng Zhan ◽  
Shu-dian Lin ◽  
Ying Liu ◽  
Yu-wei Zhan ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Viability ◽  
Therapeutic Effect ◽  
Inhibitory Effect ◽  
Flow Cytometry Analysis ◽  
Cellular Models ◽  
Positive Therapeutic Effect ◽  
Apoptosis Index

IntroductionIt has been reported that the NF-κB and MMP-9 signaling pathways were involved in the pathogenesis of osteoarthritis (OA), while the treatment of OA by YSY01 could inhibit the proteasome activity. Therefore, we aimed to study the therapeutic effect of YSY01A treatment on OA via interfering with expression of NF-κB and MMP-9.Material and methodsWestern blot analysis and immunohistochemistry (IHC) assays were used to measure the expression of NF-κB and MMP-9 in animal models established via SH treatment or cellular models established via sodium nitroprusside (SNP) treatment. MTT assay and flow cytometry analysis were performed to observe the effect of YSY01 treatment on cell viability and apoptosis.ResultsThe decreased expression of NF-κB and MMP-9 was observed in OA rabbits and cells treated by YSY01A, thus indicating the inhibitory effect of YSY01A on NF-κB and MMP-9 expression. And YSY01A exhibited a positive therapeutic effect on OA both in vivo and in vitro by inhibiting the expression of NF-κB and MMP-9. Meanwhile, YSY01A treatment could increase cell viability to a certain degree and decrease the apoptosis index, which suggested the application of YSY01A in OA therapy.ConclusionsThe levels of NF-κB and MMP-9 which were associated with aggravated apoptosis were up-regulated in OA models in vivo and in vitro. YSY01A treatment could down-regulate the expression of NF-κB and MMP-9 and inhibit cell apoptosis, thus reducing the severity of OA.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

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