Glutathione S-transferase P1 (GSTP1) directly influences platinum drug chemosensitivity in ovarian tumour cell lines

Title	Glutathione S-transferase P1 (GSTP1) directly influences platinum drug chemosensitivity in ovarian tumour cell lines
Authors	L Sawers, M J Ferguson, B R Ihrig, H C Young, P Chakravarty, C R Wolf, G Smith
Magazine	British Journal of Cancer
Date	07/10/2014
DOI	10.1038/bjc.2014.386
Introduction	Chemotherapy effectiveness in ovarian cancer can be hindered by drug resistance, potentially due to changes in drug metabolism. Specifically, platinum drugs are metabolised by glutathione S-transferase P1 (GSTP1), which is expressed variably in ovarian tumours. This study introduces innovative ovarian tumour cell line models to examine how different levels of GSTP1 expression affect chemosensitivity. Utilising A2780 and cisplatin-resistant A2780DPP cells, GSTP1 was stably deleted and its expression significantly reduced. MTT assays determined sensitivity to chemotherapy drugs. Illumina HT-12 expression arrays and qRT-PCR analysis identified differentially expressed genes in GSTP1 knockdown cells, with pathway changes predicted by MetaCore analysis. FACS analysis assessed cell cycle changes, while Boyden chamber-based assays evaluated invasion and migration. Results indicated that GSTP1 knockdown specifically altered chemosensitivity to cisplatin and carboplatin, with no effect on cell cycle progression but a significant reduction in cell invasion and migration. Several novel GSTP1 target genes and potential platinum chemotherapy response biomarkers were identified. GSTP1 plays a critical role in the metabolism of cisplatin and carboplatin in ovarian cancer cells, suggesting that varying GSTP1 expression among tumours could influence patient response to platinum-based chemotherapy.
Quote	L Sawers, M J Ferguson and B R Ihrig et al. Glutathione S-transferase P1 (GSTP1) directly influences platinum drug chemosensitivity in ovarian tumour cell lines. British Journal of Cancer. 2014. Vol. 111(6):1150-1158. DOI: 10.1038/bjc.2014.386
Element	Platinum (Pt)
Industry	Pharmaceutical Industry