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...

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Bibliographic Details
Published in:Anticancer research 2012-10, Vol.32 (10), p.4277-4286
Main Authors: LEPLEUX, Charlotte, ABEILARD-LEMOISSON, Edwige, DUVAL, Maryline, ICARD, Philippe, LINCET, Hubert
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Apoptosis Regulatory Proteins - biosynthesis
Bcl-2-Like Protein 11
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation - drug effects
Cisplatin - pharmacology
Drug Resistance, Neoplasm - genetics
Female
Female genital diseases
Gene Silencing
Gynecology. Andrology. Obstetrics
Humans
Medical sciences
Membrane Proteins - biosynthesis
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Phosphoglycerate Kinase - antagonists & inhibitors
Phosphoglycerate Kinase - genetics
Proto-Oncogene Proteins - biosynthesis
RNA, Small Interfering - genetics
Transfection
Tumors
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Summary: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.
ISSN:0250-7005
1791-7530