Transforming growth factor β is a pleiotropic cytokine which inhibits cell growth, induces cellular differentiation, and can lead to cellular apoptosis under certain conditions. TGF-β is also involved in epithelial-mesenchymal transition (EMT), a phenomenon by which cells acquire a dedifferentiated phenotype and gain motility and invasive properties. In the present study, we investigated the impact of TGF-β1 on p53 mediated cellular signalling in ovarian cancer cell lines in response to cisplatin. Four cell lines with different p53 status: A2780 (wild-type p53), A2780CP (derived from A2780, resistant to cisplatin, one p53 allele mutated V172F and one p53 allele wild-type), OVCAR-3 (p53 mutated R248Q) and SKOV-3 (p53 negative) were used in the present study. Cells were co-treated with TGF-β1 (10ng/mL) and cisplatin (10μM) for 24 hours and protein levels were analysed by western blotting. Our results show that TGF-β1 inhibits cisplatin-induced apoptosis in SKOV-3 cells as demonstrated by reduced PARP cleavage and caspase-3 activation. However, the inhibition of cisplatin-induced apoptosis was not observed in cells with wild type or mutated p53. Co-treatment of TGF-β1 and cisplatin decreased the levels of phosphorylated/active Akt compared to cisplatin alone, suggesting that TGF-β1 promotes cisplatin-induced apoptosis in A2780 cells in part through p53. In addition, Mdm2 was cleaved in response to cisplatin treatment only in p53 wild-type expressing A2780 cells. The levels of the caspase inhibitor XIAP were also decreased in A2780 cells when treated with cisplatin. Together, these results suggest that TGF-β1 promotes apoptosis when used in combination with cisplatin in p53 wild-type ovarian cancer cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4901. doi:1538-7445.AM2012-4901