siPGK1 sensitizes chemoresistant human ovarian cancer cell lines to cisplatin.

Enhanced glycolysis provides essential intermediates for cancer cell proliferation. Its inhibition could be a promising approach for destroying tumors, especially those developing in hypoxic conditions, which are presumably the most chemoresistant. In hypoxic cells, glycolysis provides the main part of ATP. Phosphoglycerate kinase-1 (PGK1) catalyzes a crucial reaction of glycolysis that reconstitutes the two molecules of ATP previously consumed. PGK1 inhibition could arrest growth or kill hypoxic and/or chemoresistant cells. We tested siPGK1 transfection in two human ovarian cancer cells lines of increasing chemoresistance, and showed that: Expression of PGK1 was significantly reduced and associated with blockade of cell growth in the G(1) phase; siPGK1 associated with cisplatin was more effective than cisplatin-alone at inhibiting proliferation of chemoresistant cells; siPGK1 -alone and -associated with cisplatin strongly increased expression of the BH3-only pro-apoptotic protein BCL-2 Interacting Mediator of cell death (BIM). PGK1 might be a key target for sensitizing chemoresistant cells to cisplatin.