scholarly journals Multi‑drug‑resistance efflux in cisplatin‑naive and cisplatin‑exposed A2780 ovarian cancer cells responds differently to cell culture dimensionality

2021 ◽  
Vol 15 (2) ◽  
Author(s):  
Vasilij Koshkin ◽  
Mariana De Oliveira ◽  
Chun Peng ◽  
Laurie   Ailles ◽  
Geoffrey Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Culture ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Multi Drug Resistance ◽  
Ovarian Cancer Cells

scholarly journals Heat Shock Protein 90 Triggers Multi-Drug Resistance of Ovarian Cancer via AKT/GSK3β/β-Catenin Signaling

2021 ◽  
Vol 11 ◽  
Author(s):  
Lan Yin ◽  
Yuhan Yang ◽  
Wanglong Zhu ◽  
Yu Xian ◽  
Zhengyu Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Heat Shock ◽  
Cancer Cells ◽  
Transcriptional Activity ◽  
Heat Shock Protein 90 ◽  
Multi Drug Resistance ◽  
Ovarian Cancer Cells ◽  
Drug Resistant ◽  
Resistance Protein

Ovarian cancer is the most lethal gynaecologic tumor, with which multi-drug resistance as the major therapeutic hindrance. Heat shock protein 90 (Hsp90) has been involved in cancer malignant behaviors. However, its role and mechanism in multi-drug resistance of ovarian cancer remains poorly understood. Our results demonstrated that Hsp90 was overexpressed in multi-drug resistant ovarian cancer cells. Hsp90 downregulation by shHsp90 or inhibitor BIIB021 increased the sensitivity of multi-drug resistant ovarian cancer cells to paclitaxel and cisplatin, and augmented the drugs-induced apoptosis. Hsp90 positively regulated the expressions of multi-drug resistance protein 1 (P-gp/MDR1), breast cancer resistance protein (BCRP), Survivin and Bcl-2 expressions closely associated with multi-drug resistance. Moreover, overexpression of Hsp90 promoted β-catenin accumulation, while Hsp90 downregulation decreased the accumulation, nuclear translocation and transcriptional activity of β-catenin. We also identified that β-catenin was responsible for Hsp90-mediated expressions of P-gp, BCRP, Survivin, and Bcl-2. Furthermore, Hsp90 enhanced the AKT/GSK3β signaling, and AKT signaling played a critical role in Hsp90-induced accumulation and transcriptional activity of β-catenin, as well as multi-drug resistance to paclitaxel and cisplatin. In conclusion, Hsp90 enhanced the AKT/GSK3β/β-catenin signaling to induce multi-drug resistance of ovarian cancer. Suppressing Hsp90 chemosensitized multi-drug resistant ovarian cancer cells via impairing the AKT/GSK3β/β-catenin signaling, providing a promising therapeutic strategy for a successful treatment of ovarian cancer.

scholarly journals Poly(adenosine diphosphate ribose) polymerase inhibitors induce autophagy‐mediated drug resistance in ovarian cancer cells, xenografts, and patient‐derived xenograft models

Cancer ◽  
2019 ◽  
Vol 126 (4) ◽  
pp. 894-907 ◽  
Author(s):  
Janice M. Santiago‐O’Farrill ◽  
S. John Weroha ◽  
Xiaonan Hou ◽  
Ann L. Oberg ◽  
Ethan P. Heinzen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Adenosine Diphosphate ◽  
Ovarian Cancer Cells ◽  
Patient Derived Xenograft ◽  
Polymerase Inhibitors ◽  
Xenograft Models

scholarly journals Mutual Expression of ALDH1A1, LOX, and Collagens in Ovarian Cancer Cell Lines as Combined CSCs- and ECM-Related Models of Drug Resistance Development

2018 ◽  
Vol 20 (1) ◽  
pp. 54 ◽  
Author(s):  
Karolina Sterzyńska ◽  
Andrzej Klejewski ◽  
Karolina Wojtowicz ◽  
Monika Świerczewska ◽  
Marta Nowacka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Matrix ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Lysyl Oxidase ◽  
Resistant Cell ◽  
Pcr Analysis ◽  
Ovarian Cancer Cells

A major contributor leading to treatment failure of ovarian cancer patients is the drug resistance of cancer cell. CSCs- (cancer stem cells) and ECM (extracellular matrix)-related models of drug resistance are described as independently occurring in cancer cells. Lysyl oxidase (LOX) is another extracellular protein involved in collagen cross-linking and remodeling of extracellular matrix and has been correlated with tumor progression. The expression of LOX, COL1A2, COL3A1, and ALDH1A1 was performed in sensitive (A2780, W1) and resistant to paclitaxel (PAC) (A2780PR1 and W1PR2) and topotecan (TOP) (W1TR) cell lines at the mRNA (real-time PCR analysis) and protein level (Western blot and immunofluorescence analysis). The ALDH1A1 activity was measured with the ALDEFLUOR test and flow cytometry analysis. The protein expression in ovarian cancer tissues was determined by immunohistochemistry. We observed an increased expression of LOX and collagens in PAC and TOP resistant cell lines. Subpopulations of ALDH1A1 positive and negative cells were also noted for examined cell lines. Additionally, the coexpression of LOX with ALDH1A1 and COL1A2 with ALDH1A1 was observed. The expression of LOX, collagens, and ALDH1A1 was also detected in ovarian cancer lesions. In our study LOX, ALDH1A1 and collagens were found to be coordinately expressed by cells resistant to PAC (LOX, ALDH1A1, and COL1A2) or to TOP (LOX and ALDH1A1). This represents the study where molecules related with CSCs (ALDH1A1) and ECM (LOX, collagens) models of drug resistance are described as occurring simultaneously in ovarian cancer cells treated with PAC and TOP.

Glucosamine reverses drug resistance in MRP2 overexpressing ovarian cancer cells

2020 ◽  
Vol 868 ◽  
pp. 172883 ◽  
Author(s):  
Fatemeh Valinezhad Sani ◽  
Abbasali Palizban ◽  
Fatemeh Mosaffa ◽  
Khadijeh Jamialahmadi
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Ovarian Cancer Cells

MDR1 and MDR3 genes and drug resistance to cisplatin of ovarian cancer cells

2007 ◽  
Vol 27 (6) ◽  
pp. 721-724 ◽  
Author(s):  
Lirong Ren ◽  
Lan Xiao ◽  
Jianli Hu ◽  
Zhimin Li ◽  
Zehua Wang
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Ovarian Cancer Cells

scholarly journals The effect of iron on the expression levels of calcium related gene in cisplatin resistant epithelial ovarian cancer cells

2021 ◽  
Author(s):  
Bahire Kucukkaya ◽  
Demet Erdag ◽  
Fahri Akbas ◽  
Leman Yalcintepe
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Calcium Homeostasis ◽  
Ovarian Cancer Cell Line ◽  
Ovarian Cancer Cells ◽  
Gene Expressions ◽  
Iron Treatment

Aim: Anticancer drugs (chemotherapeutics) used in cancer treatment (chemotherapy) lead to drug resistance. This study was conducted to investigate the possible effect of iron on calcium homeostasis in epithelial ovarian cancer cells (MDAH-2774) and cisplatin-resistant cells of the same cell line (MDAH-2774/DDP). Methods: To develop MDAH-2774/DDP cells, MDAH-2774 (MDAH) cells were treated with cisplatin in dose increases of 5 μM between 0 μM and 70 μM. The effect of iron on the viability of MDAH and MDAH/DDP cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test at the end of 24 h incubation. Results: At increasing iron concentrations in MDAH and MDAH/DDP cells, the mRNA gene of fifteen genes [inositol 1,4,5-triphosphate receptor (IP3R)1/2/3, ryanodine receptor (RYR)1/2, sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)1/2/3, Na+/Ca2+ exchange (NCX)1/2/3, and plasma membrane Ca2+ ATPase (PMCA)1/2/3/4] associated with Ca2+ differences in expression were determined by quantitative reverse transcription-polymerase chain reaction. Changes in IP3R2, RYR1, SERCA2, NCX3, PMCA1, and PMCA3 gene expressions were observed in iron treatment of MDAH/DDP cells, while changes were detected in iron treatment of MDAH cells in IP3R1/2/3, RYR1/2, SERCA1/2/3, NCX2/3, and PMCA1 expressions. Conclusions: This changes in the expression of calcium channels, pumps, and exchange proteins in the epithelial ovarian cancer cell line and in cisplatin-resistant epithelial ovarian cancer cells suggest that iron may have an important role in regulating calcium homeostasis. Due to differences in the expression of genes that play of an important role in the regulation of calcium homeostasis in the effect of iron, drug resistance can be prevented by introducing a new perspective on the use of inhibitors and activators of these genes and thus cytostatic treatment strategies.

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