Mechanisms of apoptosis and autophagy in chemoresistant ovarian cancer cells

Bennacer, Ahlem, Roberts, Helen C. ORCID logoORCID: https://orcid.org/0000-0003-1974-0319 and Stordal, Britta K. ORCID logoORCID: https://orcid.org/0000-0002-7892-951X (2018) Mechanisms of apoptosis and autophagy in chemoresistant ovarian cancer cells. In: Research Degrees Students' Summer Conference, 04 Sept 2018, Middlesex University, London, UK. . [Conference or Workshop Item]

Abstract

Introduction: Ovarian Cancer is the most lethal gynaecologic malignancy, with epithelial ovarian cancer accounting for around 90% of all cases. Most patients present with advanced stage disease at the time of diagnosis, resulting in a poor prognosis and a 30% 5-year survival rate. Treatment is usually comprised of surgery and combination chemotherapy, most commonly using carboplatin and taxol, but one of the major contributing factors to the disease’s poor prognosis is chemoresistance. Several cellular pathways have been found to be involved in chemoresistance, but their mechanisms of action are still not fully understood. PLAC8, MAP3K15, Bcl-2 and Bcl-xl have been previously identified as anti-apoptotic proteins of interest, due to their overexpression in carboplatin- and taxol-resistant cell lines. Interestingly, PLAC8 has also been found to be involved in autophagy, suggesting the potential involvement of autophagy in ovarian cancer chemoresistance. This research aims to further investigate the role of both apoptosis and autophagy in ovarian cancer chemoresistance, through measuring gene expression, protein expression and the effects of gene knockdown on drug sensitivity, apoptosis and autophagy in an ovarian cancer cell line. This is the first time PLAC8 will be investigated in ovarian cancer chemoresistance, providing novel research to aid in the understanding of its mechanism of action. Quantitative PCR (qPCR) was used to analyse the gene expression of previously identified genes of interest, including PLAC8, MAP3K15, Bcl-2 and Bcl-xl, in the following ovarian cancer cell lines:- UPN251 (sensitive to chemotherapy), UPN251-7C (carboplatin-resistant) and UPN251-7T (taxol-resistant). Western blots will be run to confirm the presence or absence of these proteins of interest in the 3 cell lines, both with and without drug treatment. MAP3K15 and PLAC8 expression was found to be significantly increased (~7-fold ±1; p<0.001 and ~8-fold ±1.6; p<0.001, respectively) in the 2 chemoresistant cell lines compared to the chemosensitive cell line. The protein expression of PLAC8 was found to be consistent with its increased gene expression in the chemoresistant cell lines, suggesting the involvement of PLAC8 in ovarian cancer chemoresistance. Since PLAC8 has been found to be linked with autophagy, the involvement of previously identified autophagy markers will also be investigated through gene and protein analysis.

Item Type: Conference or Workshop Item (Presentation)
Sustainable Development Goals:
Theme:
Research Areas: A. > School of Science and Technology > Natural Sciences > Biomarkers for Cancer group
Item ID: 35489
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Depositing User: Britta Stordal
Date Deposited: 25 Jul 2022 17:31
Last Modified: 25 Jul 2022 17:31
URI: https://eprints.mdx.ac.uk/id/eprint/35489

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