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.
University of Caen Basse-Normandie, BioTICLA EA 4656, IFR146 ICORE, Cancer Center François Baclesse, Caen, France.
Charlotte
C
Lepleux
Edwige
E
Abeilard-Lemoisson
Maryline
M
Duval
Philippe
P
Icard
Hubert
H
Lincet
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D000072224:Bcl-2-Like Protein 11; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010735:Phosphoglycerate Kinase / Q000037:antagonists & inhibitors* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C577282:PGK1 protein, human; D010735:Phosphoglycerate Kinase; D002945:Cisplatin