scholarly journals Soft drug-resistant ovarian cancer cells invade via two distinct mechanisms utilizing myosin IIB

2017 ◽  
Author(s):  
Aastha Kapoor ◽  
Bhushan Thakur ◽  
Melissa Monteiro ◽  
Alakesh Das ◽  
Sejal Desai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Drug Resistant ◽  
Protease Inhibition ◽  
Invasion Mechanisms ◽  
Soft Drug ◽  
Metalloproteinase 9 ◽  
Independent Mode ◽  
Dual Drug

The failure of chemotherapeutic drugs in treatment of various cancers is attributed to the acquisition of drug resistance. However, the invasion mechanisms of drug-resistant cancer cells remains incompletely understood. Here we address this question from a biophysical perspective by mapping the phenotypic alterations in ovarian cancer cells (OCCs) resistant to cisplatin and paclitaxel. We show that cisplatin-resistant (CisR), paclitaxel-resistant (PacR) and dual drug-resistant (i.e., resistant to both drugs) OCCs are softer and more contractile than drug-sensitive cells. Protease inhibition suppresses invasion of CisR cells but not of PacR and dual cells, suggesting protease-dependent mode of invasion in CisR cells and protease-independent mode in PacR and dual cells. Despite these differences, actomyosin contractility, mediated by the RhoA-ROCK2-Myosin IIB signaling pathway regulates both modes of invasion. Myosin IIB modulates matrix metalloproteinase-9 (MMP-9) secretion in CisR cells and nuclear squeezing in PacR and dual cells, thereby highlighting its importance as a potential therapeutic target for treatment of drug-resistant ovarian cancer cells.

scholarly journals Soft drug-resistant ovarian cancer cells migrate via two distinct mechanisms utilizing myosin II-based contractility

2018 ◽  
Vol 1865 (2) ◽  
pp. 392-405 ◽  
Author(s):  
Aastha Kapoor ◽  
Amlan Barai ◽  
Bhushan Thakur ◽  
Alakesh Das ◽  
Sejal R. Patwardhan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Myosin Ii ◽  
Ovarian Cancer Cells ◽  
Drug Resistant ◽  
Soft Drug

Kuguacin J isolated from bitter melon leaves modulates paclitaxel sensitivity in drug-resistant human ovarian cancer cells

2017 ◽  
Vol 71 (4) ◽  
pp. 693-702 ◽  
Author(s):  
Pornsiri Pitchakarn ◽  
Sonthaya Umsumarng ◽  
Sariya Mapoung ◽  
Pisamai Ting ◽  
Piya Temviriyanukul ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Bitter Melon ◽  
Drug Resistant

scholarly journals Enzyme-Regulated Supramolecular Assemblies of Cholesterol Conjugates against Drug-Resistant Ovarian Cancer Cells

2016 ◽  
Vol 138 (34) ◽  
pp. 10758-10761 ◽  
Author(s):  
Huaimin Wang ◽  
Zhaoqianqi Feng ◽  
Dongdong Wu ◽  
Keith J. Fritzsching ◽  
Mike Rigney ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Supramolecular Assemblies ◽  
Ovarian Cancer Cells ◽  
Drug Resistant

scholarly journals RNAi-mediated knockdown of the CLN3 gene inhibits proliferation and promotes apoptosis in drug-resistant ovarian cancer cells

2015 ◽  
Vol 12 (5) ◽  
pp. 6635-6641 ◽  
Author(s):  
DONGWEI MAO ◽  
JIANHUA CHE ◽  
SHIYU HAN ◽  
HONGHUI ZHAO ◽  
YUMEI ZHU ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Drug Resistant

scholarly journals CPEB4-Promoted Paclitaxel Resistance in Ovarian Cancer In Vitro Relies on Translational Regulation of CSAG2

2021 ◽  
Vol 11 ◽  
Author(s):  
Yaqing Zhang ◽  
Hongyun Gan ◽  
Fei Zhao ◽  
Xiaomei Ma ◽  
Xiaofeng Xie ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Rna Binding ◽  
Ovarian Cancer Cells ◽  
Drug Resistant ◽  
Paclitaxel Resistance ◽  
Cytoplasmic Polyadenylation

Background: Drug resistance is a major obstacle in chemotherapy for ovarian cancer, wherein the up regulation of drug-resistant genes plays an important role. The cytoplasmic polyadenylation element binding protein 4 (CPEB4) is an RNA binding protein that controls mRNA cytoplasmic polyadenylation and translation.Methods: The expression of CPEB4 in paclitaxel-resistant ovarian cancer cell lines and recurrent ovarian tumors relative to counterparts was determined by qRT-PCR, Western blotting and immunohistochemistry. The response to paclitaxel treatment was evaluated by cellular viability test and colony formation assay. RNA immunoprecipitation and poly(A) tail test were applied to examine the levels of RNA binding and cytoplasmic polyadenylation.Results: CPEB4 is elevated in paclitaxel-resistant ovarian cancer cells and recurrent ovarian tumors treated with paclitaxel-based chemotherapy. In addition, CPEB4 overexpression promotes paclitaxel resistance in ovarian cancer cells in vitro, and vice versa, CPEB4 knockdown restores paclitaxel sensitivity, indicating that CPEB4 confers paclitaxel resistance in ovarian cancer cells. Mechanistically, CPEB4 binds with the taxol (paclitaxel)-resistance-associated gene-3 (TRAG-3/CSAG2) mRNAs and induces its expression at a translational level. Moreover, CSAG2 expression is upregulated in paclitaxel-resistant ovarian carcinoma and cancer cell lines, and more importantly, siRNA-mediated CSAG2 knockdown overtly attenuates CPEB4-mediated paclitaxel resistance.Conclusion: This study suggests that the drug-resistant protein CSAG2 is translationally induced by CPEB4, which underlies CPEB4-promoted paclitaxel resistance in ovarian cancer in vitro. Thus, interfering CPEB4/CSAG2 axis might be of benefit to overcome paclitaxel-resistant ovarian cancer.

scholarly journals EfficientIn VitroTRAIL-Gene Delivery in Drug-Resistant A2780/DDP Ovarian Cancer Cell Line via Magnetofection

2011 ◽  
Vol 2011 ◽  
pp. 1-7
Author(s):  
Fang Li ◽  
Sumei Niu ◽  
Jing Sun ◽  
Huaishi Zhu ◽  
Qiujie Ba ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Gene Transfection ◽  
Ovarian Cancer Cells ◽  
Drug Resistant

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) presents great promise as an anticancer agent for human cancer therapy. In this study, a magnetofection agent (polyMAG-l000) was evaluated forin vitrodelivery of TRAIL gene towards drug-resistant A2780/DDP ovarian cancer cells. Transfection experiments showed that polyMAG-l000 was able to transfect A2780/DDP cellsin vitro, leading to a higher level of TRAIL gene expression in the presence of a static magnetic field as compared to other transfection agent, such as Lipofectamine 2000. TRAIL gene expression in the A2780/DDP cells was also confirmed by Western blot analysis. Moreover, the TRAIL gene expression exhibited remarkable decrease in the cell viability, as determined by MTT assay. Importantly, PolyMAG-l000-mediated TRAIL gene transfection in the presence of anticancer drug cisplatin (CDDP) induced much higher percentages of apoptotic A2780/DDP cells, compared to TRAIL gene transfection or CDDP treatment alone. A further study by Western blot analysis indicated that cytochromecrelease and caspase-9 cleavage pathway were associated with the initiation of the apoptosis in A2780/DDP cells. The results of this study indicate that polyMAG-l000 can be used as an efficient agent for TRAIL gene transfection in ovarian cancer cells.

scholarly journals Nano-mechanical Reinforcement in Drug-Resistant Ovarian Cancer Cells

2015 ◽  
Vol 38 (3) ◽  
pp. 389-395 ◽  
Author(s):  
Young Ho Seo ◽  
Yoo-na Jo ◽  
Yong Jin Oh ◽  
Soyeun Park
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Drug Resistant ◽  
Mechanical Reinforcement

scholarly journals A Co-Delivery System of Curcumin and p53 for Enhancing the Sensitivity of Drug-Resistant Ovarian Cancer Cells to Cisplatin

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2621
Author(s):  
Xinli Guo ◽  
Zhou Fang ◽  
Min Zhang ◽  
Deyu Yang ◽  
Shuyue Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Delivery System ◽  
Self Assembly ◽  
Messenger Rna ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Ovarian Cancer Cells ◽  
Drug Resistant ◽  
Sensitizing Effect

In order to enhance the sensitivity of drug-resistant ovarian cancer cells to cisplatin (DDP), a co-delivery system was designed for simultaneous delivery of curcumin (CUR) and p53 DNA. Firstly, the bifunctional peptide K14 composed of tumor targeting peptide (tLyP-1) and nuclear localization signal (NLS) was synthesized. A nonviral carrier (PEI-K14) was synthesized by cross-linking low molecular weight polyethyleneimine (PEI) with K14. Then, CUR was coupled to PEI-K14 by matrix metalloproteinase 9 (MMP9)-cleavable peptide to prepare CUR-PEI-K14. A co-delivery system, named CUR-PEI-K14/p53, was obtained by CUR-PEI-K14 and p53 self-assembly. Furthermore, the physicochemical properties and gene transfection efficiency were evaluated. Finally, ovarian cancer cisplatin-resistant (SKOV3-DDP) cells were selected to evaluate the effect of CUR-PEI-K14/p53 on enhancing the sensitivity of drug-resistant cells to DDP. The CUR-PEI-K14/DNA complexes appeared uniformly dispersed and spherical. The particle size was around 20–150 nm and the zeta potential was around 18–37 mV. It had good stability, high transfection efficiency, and low cytotoxicity. CUR-PEI-K14/p53 could significantly increase the sensitivity of SKOV3-DDP cells to DDP, and this effect was better as combined with DDP. The sensitizing effect might be related to the upregulation of p53 messenger RNA (mRNA), the downregulation of P-glycoprotein (P-gp) mRNA, and the upregulation of BCL2-Associated X (bax) mRNA. CUR-PEI-K14/p53 can be used as an effective strategy to enhance the sensitivity of drug-resistant ovarian cancer cells to DDP.

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