Mechanisms of apoptosis and autophagy in chemoresistant ovarian cancer cells

Conference item

Bennacer, A., Roberts, H. and Stordal, B. 2018. Mechanisms of apoptosis and autophagy in chemoresistant ovarian cancer cells. Research Degrees Students' Summer Conference. Middlesex University, London, UK 04 Sep 2018
TitleMechanisms of apoptosis and autophagy in chemoresistant ovarian cancer cells
AuthorsBennacer, A., Roberts, H. and Stordal, B.
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.

Sustainable Development Goals3 Good health and well-being
Middlesex University ThemeHealth & Wellbeing
Research GroupBiomarkers for Cancer group
ConferenceResearch Degrees Students' Summer Conference
Publication dates
Print04 Sep 2018
Publication process dates
Deposited25 Jul 2022
Accepted04 Aug 2018
Output statusPublished
LanguageEnglish
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D’Adhemar, C., Spillane, C., Gallagher, M., Bates, M., Costello, K., Barry-O'Crowley, J., Haley, K., Kernan, N., Murphy, C., Smyth, P., O'Byrne, K., Pennington, S., Cooke, A., Ffrench, B., Martin, C., O'Donnell, D., Hennessy, B., Stordal, B., Finn, S., McCann, A., Gleeson, N., D'Arcy, T., Flood, B., O'Neill, L., Sheils, O., O'Toole, S. and O'Leary, J. 2014. The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer. PLoS ONE. 9 (6), pp. 1-15. https://doi.org/10.1371/journal.pone.0100816
OvMark: a user-friendly system for the identification of prognostic biomarkers in publically available ovarian cancer gene expression datasets
Madden, S., Clarke, C., Stordal, B., Carey, M., Broaddus, R., Gallagher, W., Crown, J., Mills, G. and Hennessy, B. 2014. OvMark: a user-friendly system for the identification of prognostic biomarkers in publically available ovarian cancer gene expression datasets. Molecular Cancer. 13 (1), pp. 1-11. https://doi.org/10.1186/1476-4598-13-241
PARP inhibitors as P-glyoprotein substrates
Lawlor, D., Martin, P., Busschots, S., Thery, J., O'Leary, J.J., Hennessy, B.T. and Stordal, B. 2014. PARP inhibitors as P-glyoprotein substrates. Journal of Pharmaceutical Sciences. 103 (6), pp. 1913-1920. https://doi.org/10.1002/jps.23952
Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells
Doherty, B., Lawlor, D., Gillet, J., Gottesman, M., O'Leary, J. and Stordal, B. 2014. Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells. Anticancer Research. 34 (1), pp. 503-507.
In vitro development of chemotherapy and targeted therapy drug-resistant cancer cell lines: a practical guide with case studies
McDermott, M., Eustace, A., Busschots, S., Breen, L., Crown, J., Clynes, M., O'Donovan, N. and Stordal, B. 2014. In vitro development of chemotherapy and targeted therapy drug-resistant cancer cell lines: a practical guide with case studies. Frontiers in Oncology. 4, pp. 1-16. https://doi.org/10.3389/fonc.2014.00040
Enhanced immunoreceptor tyrosine-based activation motif signaling is related to pathological bone resorption during critical illness
Vanhees, I., Gunst, J., Janssens, T., Wauters, A., Van Herck, E., Van Cromphaut, S., Van den Berghe, G. and Owen, H. 2013. Enhanced immunoreceptor tyrosine-based activation motif signaling is related to pathological bone resorption during critical illness. Hormone and Metabolic Research. 45 (12), pp. 862-9. https://doi.org/10.1055/s-0033-1351290
BRCA1/2 mutation analysis in 41 ovarian cell lines reveals only one functionally deleterious BRCA1 mutation
Stordal, B., Timms, K., Farrelly, A., Gallagher, D., Busschots, S., Renaud, M., Thery, J., Williams, D., Potter, J., Tran, T., Korpanty, G., Cremona, M., Carey, M., Li, J., Li, Y., Aslan, O., O'Leary, J., Mills, G. and Hennessy, B. 2013. BRCA1/2 mutation analysis in 41 ovarian cell lines reveals only one functionally deleterious BRCA1 mutation. Molecular Oncology. 7 (3), pp. 567-79. https://doi.org/10.1016/j.molonc.2012.12.007
Critical illness-related bone loss is associated with osteoclastic and angiogenic abnormalities
Owen, H., Vanhees, I., Solie, L., Roberts, S., Wauters, A., Luyten, F., Van Cromphaut, S. and Van den Berghe, G. 2012. Critical illness-related bone loss is associated with osteoclastic and angiogenic abnormalities. Journal of Bone and Mineral Research. 27 (7), pp. 1541-1552. https://doi.org/10.1002/jbmr.1612
Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein
Stordal, B., Hamon, M., McEneaney, V., Roche, S., Gillet, J., O'Leary, J., Gottesman, M. and Clynes, M. 2012. Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein. PLoS ONE. 7 (7), pp. 1-13. https://doi.org/10.1371/journal.pone.0040717
Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer
Dudziec, E., Miah, S., Choudhry, H., Owen, H., Blizard, S., Glover, M., Hamdy, F. and Catto, J. 2011. Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer. Clinical Cancer Research. 17 (6), pp. 1287-1296. https://doi.org/10.1158/1078-0432.CCR-10-2017
Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review
Murphy, M. and Stordal, B. 2011. Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review. Drug Resistance Updates. 14 (3), pp. 177-190. https://doi.org/10.1016/j.drup.2011.02.004
Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells
Egan, K., Crowley, D., Smyth, P., O'Toole, S., Spillane, C., Martin, C., Gallagher, M., Canney, A., Norris, L., Conlon, N., McEvoy, L., Ffrench, B., Stordal, B., Keegan, H., Finn, S., McEneaney, V., Laios, A., Ducrée, J., Dunne, E., Smith, L., Berndt, M., Sheils, O., Kenny, D. and O'Leary, J. 2011. Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells. PLoS ONE. 6 (10). https://doi.org/10.1371/journal.pone.0026125
Low frequency of epigenetic events in urothelial tumours from young patients
Catto, J., Owen, H., Giedl, J., Wild, P., Fine, S., Epstein, J., Humphrey, P., Dehner, L., Amin, M., Blaszyk, H., Hughes, D., Hartmann, A. and Stoehr, R. 2010. Low frequency of epigenetic events in urothelial tumours from young patients. European Urology Supplements. 9 (2), pp. 260-261. https://doi.org/10.1016/S1569-9056(10)60798-1
Low frequency of epigenetic events in urothelial tumors in young patients
Owen, H., Giedl, J., Wild, P., Fine, S., Humphrey, P., Dehner, L., Amin, M., Epstein, J., Blaszyk, H., Hughes, D., Hartmann, A., Stoehr, R. and Catto, J. 2010. Low frequency of epigenetic events in urothelial tumors in young patients. The Journal of Urology. 184 (2), pp. 459-463. https://doi.org/10.1016/j.juro.2010.03.131
Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo
Owen, H., Ahmed, S. and Farquharson, C. 2009. Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo. Calcified Tissue International and Musculoskeletal Research. 85 (4), pp. 326-334. https://doi.org/10.1007/s00223-009-9276-0
Distinct microRNA alterations characterize high- and low-grade bladder cancer
Catto, J., Miah, S., Owen, H., Bryant, H., Myers, K., Dudziec, E., Larré, S., Milo, M., Rehman, I., Rosario, D., Di Martino, E., Knowles, M., Meuth, M., Harris, A. and Hamdy, F. 2009. Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Research. 69 (21), pp. 8472-8481. https://doi.org/10.1158/0008-5472.CAN-09-0744
ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair
Stordal, B. and Davey, R. 2009. ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair. Cancer Chemotherapy and Pharmacology. 63 (4), pp. 661-672. https://doi.org/10.1007/s00280-008-0783-x
Citations, citations everywhere but did anyone read the paper? [Letter to the Editor]
Stordal, B. 2009. Citations, citations everywhere but did anyone read the paper? [Letter to the Editor]. Colloids and surfaces. B, Biointerfaces. 72 (2), pp. 312 -312. https://doi.org/10.1016/j.colsurfb.2009.04.001
A systematic review of genes involved in the inverse resistance relationship between cisplatin and paclitaxel chemotherapy: role of BRCA1
Stordal, B. and Davey, R. 2009. A systematic review of genes involved in the inverse resistance relationship between cisplatin and paclitaxel chemotherapy: role of BRCA1. Current Cancer Drug Targets. 9 (3), pp. 354-365. https://doi.org/10.2174/156800909788166592
Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes
Owen, H., Roberts, S., Ahmed, S. and Farquharson, C. 2008. Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes. American Journal of Physiology - Endocrinology and Metabolism. 294 (6), pp. E1023-E1034. https://doi.org/10.1152/ajpendo.00586.2007
Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1
Roberts, S., Owen, H. and Farquharson, C. 2008. Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1. Biochemical and Biophysical Research Communications. 371 (4), pp. 872-876. https://doi.org/10.1016/j.bbrc.2008.04.163
Platinum resistance needs the mythbusters [Letter to the Editor]
Stordal, B. and Davey, R. 2008. Platinum resistance needs the mythbusters [Letter to the Editor]. Toxicology letters. 180 (3), p. 230. https://doi.org/10.1016/j.toxlet.2008.07.003
A 39 kDa fragment of endogenous ASK1 suggests specific cleavage not degradation by the proteasome
Stordal, B. and Davey, R. 2008. A 39 kDa fragment of endogenous ASK1 suggests specific cleavage not degradation by the proteasome. IUBMB Life. 60 (3), pp. 180-184. https://doi.org/10.1002/iub.24
Identification and functional involvement of lipocalin 2 in glucocorticoid-induced growth retardation
Owen, H., Ahmed, S. and Farquharson, C. 2007. Identification and functional involvement of lipocalin 2 in glucocorticoid-induced growth retardation. 29th Annual Meeting of the American Society for Bone and Mineral Research. Honolulu, HI 16 - 19 Sep 2007 Wiley.
The role of P21CIP1/WAF1 in glucocorticoid induced growth retardation
Owen, H., Ahmed, S. and Farquharson, C. 2007. The role of P21CIP1/WAF1 in glucocorticoid induced growth retardation. 2007 Annual Meeting of the Bone Research Society. Southampton, UK 03 - 05 Jul 2007 Wiley.
Identification of lipocalin 2, a novel glucocorticoid responsive gene in growth plate chondrocytes
Owen, H., Ahmed, S. and Farquharson, C. 2007. Identification of lipocalin 2, a novel glucocorticoid responsive gene in growth plate chondrocytes. 2007 Annual Meeting of the Bone Research Society. Southampton, UK 03 - 05 Jul 2007 Wiley.
The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438
Owen, H., Miner, J., Ahmed, S. and Farquharson, C. 2007. The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438. Molecular and Cellular Endocrinology. 264 (1-2), pp. 164-70. https://doi.org/10.1016/j.mce.2006.11.006
A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship
Stordal, B., Pavlakis, N. and Davey, R. 2007. A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship. Cancer Treatment Reviews. 33 (8), pp. 688-703. https://doi.org/10.1016/j.ctrv.2007.07.013
Understanding cisplatin resistance using cellular models
Stordal, B. and Davey, M. 2007. Understanding cisplatin resistance using cellular models. IUBMB Life. 59 (11), pp. 696-699. https://doi.org/10.1080/15216540701636287
Oxaliplatin for the treatment of cisplatin-resistant cancer: a systematic review
Stordal, B., Pavlakis, N. and Davey, R. 2007. Oxaliplatin for the treatment of cisplatin-resistant cancer: a systematic review. Cancer Treatment Reviews. 33 (4), pp. 347-357. https://doi.org/10.1016/j.ctrv.2007.01.009
Glucocorticoids stimulate p21 expression in growth plate chondrocytes
Owen, H., Ahmed, S. and Farquharson, C. 2006. Glucocorticoids stimulate p21 expression in growth plate chondrocytes. 2006 Annual Meeting of the Bone Research Society. Southampton, UK 05 - 06 Jul 2006 Wiley.
Glucocorticoids induce lipocalin 2 gene expression in growth plate chondrocytes.
Owen, H., Ahmed, S. and Farquharson, C. 2006. Glucocorticoids induce lipocalin 2 gene expression in growth plate chondrocytes. 28th Annual Meeting of the American Society for Bone and Mineral Research. Philadelphia, PA 15 - 19 Sep 2006 Wiley.
The role of the 11 beta HSD shuttle in modulating the effects of proinflammatory cytokines on the growth plate
MacRae, V., Owen, H., Ahmed, S. and Farquharson, C. 2006. The role of the 11 beta HSD shuttle in modulating the effects of proinflammatory cytokines on the growth plate. 28th Annual Meeting of the American Society for Bone and Mineral Research. Philadelphia, PA 15 - 19 Sep 2006 Wiley.
Similar chromosomal changes in cisplatin and oxaliplatin-resistant sublines of the H69 SCLC cell line are not associated with platinum resistance
Stordal, B., Peters, G. and Davey, R. 2006. Similar chromosomal changes in cisplatin and oxaliplatin-resistant sublines of the H69 SCLC cell line are not associated with platinum resistance. Genes, Chromosomes & Cancer. 45 (12), pp. 1094-105. https://doi.org/10.1002/gcc.20373
Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells
Stordal, B., Davey, M. and Davey, R. 2006. Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells. Cancer Chemotherapy and Pharmacology. 58 (2), pp. 256-265. https://doi.org/10.1007/s00280-005-0148-7