scholarly journals MDR Gene Expression Analysis of Six Drug-Resistant Ovarian Cancer Cell Lines

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Radosław Januchowski ◽  
Karolina Wojtowicz ◽  
Patrycja Sujka-Kordowska ◽  
Małgorzata Andrzejewska ◽  
Maciej Zabel
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Multiple Drug Resistance ◽  
Cancer Cell Lines ◽  
Resistant Cell ◽  
Cross Resistance ◽  
Ovarian Cancer Cell Lines

Ovarian cancer is the leading cause of death among gynaecological malignancies. Multiple drug resistance makes cancer cells insensitive to chemotherapy. In this study, we developed six primary ovarian cancer cell lines (W1MR, W1CR, W1DR, W1VR, W1TR, and W1PR) resistant to drugs such as methotrexate, cisplatin, doxorubicin, vincristine, topotecan, and paclitaxel. A chemosensitivity assay MTT test was performed to assess drug cross-resistance. Quantitative real-time polymerase chain reaction and Western blot were also performed to determine mRNA and protein expression of genes involved in chemoresistance. We observed high cross-resistance to doxorubicin, vincristine, and paclitaxel in the cell lines resistant to these agents. We also found a significant correlation between resistance to these drugs and increased expression of P-gp. Two different mechanisms of topotecan resistance were observed in the W1TR and W1PR cell lines. We did not observe any correlation between MRP2 transcript and protein levels. Cell lines resistant to agents used in ovarian cancer treatment remained sensitive to methotrexate. The main mechanisms of drug resistance were due to P-gp expression in the doxorubicin, vincristine, and paclitaxel resistant cell lines and BCRP expression in the topotecan resistant cell line.

scholarly journals Microarray-based detection and expression analysis of new genes associated with drug resistance in ovarian cancer cell lines

Oncotarget ◽  
2017 ◽  
Vol 8 (30) ◽  
pp. 49944-49958 ◽  
Author(s):  
Radosław Januchowski ◽  
Karolina Sterzyńska ◽  
Piotr Zawierucha ◽  
Marcin Ruciński ◽  
Monika Świerczewska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Expression Analysis ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
New Genes ◽  
Ovarian Cancer Cell Lines

scholarly journals Inhibition of MUS81 By siRNA Reverses Resistance to Cisplatin in Human Ovarian Cancer Cell Lines

2021 ◽  
Author(s):  
Emma C. Bourton ◽  
Sheba Adam-Zahir ◽  
Piers N. Plowman ◽  
Hussein Nahidh Al-Ali ◽  
Helen A. Foster ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Resistant Cell ◽  
Wild Type ◽  
Ovarian Cancer Cell Lines ◽  
Sirna Knockdown

Abstract Bacground: Drugs that induce DNA interstrand crosslinks form the mainstay of anticancer treatments for different cancers. These drugs are used to treat ovarian cancer which is the most prevalent gynaecological cancer. Five-year survival rates are approximately 40% and the development of drug resistant disease is an important factor in treatment failure. Methods: In this study a comprehensive evaluation of the expression and function of the site-specific endonuclease MUS81 was conducted. Using quantitative real time PCR analysis and imaging flow cytometry we determined the mRNA and protein expression of MUS81 in three ovarian cancer cell lines and two immortalised human fibroblast cell lines which had been made resistant to cisplatin by chronic exposure. siRNA knockdown of MUS81 was employed to determine the effect on overall cell survival which was assessed using clonogenic assays. Results: In the five cisplatin-resistant cell lines we observed increased MUS81 mRNA expression. In addition MUS81 protein expression in the form of discrete nuclear foci in cells was observed in all cell lines following cisplatin exposure, there being significantly more foci in cisplatin resistant cell lines. siRNA knockdown of MUS81 significantly reduced both mRNA and protein levels in two cell lines (SK-OV-3 and MRC5-SV1 – wild-type and resistant) and critically re-sensitised cisplatin resistant cells to wild-type level, determined by clonogenic assay.Conclusion: MUS81 is central to the development of cisplatin resistance in ovarian cancer cell lines. Inhibition of MUS81 restored drug sensitivity to the cells. MUS81 may be a useful therapeutic target to overcome drug resistance in ovarian and other cancers.

scholarly journals Palmatine from Unexplored Rutidea parviflora Showed Cytotoxicity and Induction of Apoptosis in Human Ovarian Cancer Cells

Toxins ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 237 ◽  
Author(s):  
Okiemute Rosa Johnson-Ajinwo ◽  
Alan Richardson ◽  
Wen-Wu Li
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Caspase 3 ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Cross Resistance ◽  
Gas Liquid Chromatography ◽  
Ovarian Cancer Cell Lines

Ovarian cancer ranks amongst the deadliest cancers in the gynaecological category of cancers. This research work aims to evaluate in vitro anti-ovarian cancer activities and identify phytochemical constituents of a rarely explored plant species—Rutidea parviflora DC. The aqueous and organic extracts of the plant were evaluated for cytotoxicity using sulforhodamine B assay in four ovarian cancer cell lines and an immortalized human ovarian epithelial (HOE) cell line. The bioactive compounds were isolated and characterized by gas/liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. Caspase 3/7 activity assay, western blotting and flow cytometry were carried out to assess apoptotic effects of active compounds. The extracts/fractions of R. parviflora showed promising anti-ovarian cancer activities in ovarian cancer cell lines. A principal cytotoxic alkaloid was identified as palmatine whose IC50 was determined as 5.5–7.9 µM. Palmatine was relatively selective towards cancer cells as it was less cytotoxic toward HOE cells, also demonstrating interestingly absence of cross-resistance in cisplatin-resistant A2780 cells. Palmatine further induced apoptosis by increasing caspase 3/7 activity, poly-ADP-ribose polymerase cleavage, and annexin V and propidium iodide staining in OVCAR-4 cancer cells. Our studies warranted further investigation of palmatine and R. parviflora extracts in preclinical models of ovarian cancer.

scholarly journals Increased Expression of Several Collagen Genes is Associated with Drug Resistance in Ovarian Cancer Cell Lines

2016 ◽  
Vol 7 (10) ◽  
pp. 1295-1310 ◽  
Author(s):  
Radosław Januchowski ◽  
Monika Świerczewska ◽  
Karolina Sterzyńska ◽  
Karolina Wojtowicz ◽  
Michał Nowicki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cell Lines ◽  
Collagen Genes

scholarly journals Analysis of MDR genes expression and cross-resistance in eight drug resistant ovarian cancer cell lines

2016 ◽  
Vol 9 (1) ◽  
Author(s):  
Radosław Januchowski ◽  
Karolina Sterzyńska ◽  
Katarzyna Zaorska ◽  
Patrycja Sosińska ◽  
Andrzej Klejewski ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Ovarian Cancer Cell Lines ◽  
Genes Expression ◽  
Mdr Genes

scholarly journals Inhibition of MUS81 by siRNA Reverses Resistance to Cisplatin in Human Ovarian Cancer Cell Lines

2021 ◽  
Author(s):  
Emma Bourton ◽  
Sheba Adam Zahir ◽  
Piers Plowman ◽  
Hussein Al-Ali ◽  
Helen Foster ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Resistant Cell ◽  
Wild Type ◽  
Ovarian Cancer Cell Lines ◽  
Sirna Knockdown

Abstract Purpose: Drugs that induce DNA interstrand crosslinks form the mainstay of anticancer treatments for different cancers. These drugs are used to treat ovarian cancer which is the most prevalent gynaecological cancer. Five-year survival rates are approximately 40% and the development of drug resistant disease is an important factor in treatment failure. Methods: In this study a comprehensive evaluation of the expression and function of the site-specific endonuclease MUS81 was conducted. Using quantitative real time PCR analysis and imaging flow cytometry we determined the mRNA and protein expression of MUS81 in three ovarian cancer cell lines and two immortalised human fibroblast cell lines which had been made resistant to cisplatin by chronic exposure. siRNA knockdown of MUS81 was employed to determine the effect on overall cell survival which was assessed using clonogenic assays. Results: In the five cisplatin-resistant cell lines we observed increased MUS81 mRNA expression. In addition MUS81 protein expression in the form of discrete nuclear foci in cells was observed in all cell lines following cisplatin exposure, there being significantly more foci in cisplatin resistant cell lines. siRNA knockdown of MUS81 significantly reduced both mRNA and protein levels in two cell lines (SK-OV-3 and MRC5-SV1 – wild-type and resistant) and critically re-sensitised cisplatin resistant cells to wild-type level, determined by clonogenic assay. Conclusion: MUS81 is central to the development of cisplatin resistance in ovarian cancer cell lines. Inhibition of MUS81 restored drug sensitivity to the cells. MUS81 may be a useful therapeutic target to overcome drug resistance in ovarian and other cancers.

Mechanisms of drug resistance to the platinum complex ZD0473 in ovarian cancer cell lines

2000 ◽  
Vol 36 (15) ◽  
pp. 1984-1990 ◽  
Author(s):  
J. Holford ◽  
P.J. Beale ◽  
F.E. Boxall ◽  
S.Y. Sharp ◽  
L.R. Kelland
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Platinum Complex ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cell Lines

scholarly journals PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations

2019 ◽  
Vol 20 (8) ◽  
pp. 2053 ◽  
Author(s):  
Świerczewska ◽  
Sterzyńska ◽  
Wojtowicz ◽  
Kaźmierczak ◽  
Iżycki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Acquired Resistance ◽  
Cancer Cell Lines ◽  
Pcr Analysis ◽  
Ovarian Cancer Cell Lines

Background: Ovarian cancer is the 7th most common cancer and 8th most mortal canceramong woman. The standard treatment includes cytoreduction surgery followed bychemotherapy. Unfortunately, in most cases, after treatment, cancer develops drug resistance.Decreased expression and/or activity of protein phosphatases leads to increased signaltransduction and development of drug resistance in cancer cells. Methods: Using sensitive (W1,A2780) and resistant ovarian cancer cell lines, the expression of Protein Tyrosine PhosphataseReceptor Type K (PTPRK) was performed at the mRNA (real‐time PCR analysis) and protein level(Western blot, immunofluorescence analysis). The protein expression in ovarian cancer tissues wasdetermined by immunohistochemistry. Results: The results showed a decreased level of PTPRKexpression in ovarian cancer cell lines resistant to cisplatin (CIS), paclitaxel (PAC), doxorubicin(DOX), topotecan (TOP), vincristine (VIN) and methotrexate (MTX). Additionally, the lowerPTPRK expression was observed in Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1)positive cancer stem cells (CSCs) population, suggesting the role of PTPRK downregulation inprimary as well as acquired resistance to cytotoxic drugs. Conclusions: These results provideimportant insights into the role of PTPRK in mechanism leading to drug resistance in ovariancancer and has raised important questions about the role of imbalance in processes ofphosphorylation and dephosphorylation.

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