PMID: 25762632Mar 13, 2015Paper

JQ1 suppresses tumor growth through downregulating LDHA in ovarian cancer

Oncotarget
Haifeng QiuVictoria L Bae-Jump

Abstract

Amplification and overexpression of c-Myc is commonly seen in human ovarian cancers, and this could be a potentially novel therapeutic target for this disease. JQ1, a selective small-molecule BET bromodomain (BRDs) inhibitor, has been found to suppress tumor progression in several cancer cell types. Using ovarian cancer cell lines, a transgenic mouse model, and primary cell cultures from human ovarian cancer tissues, we demonstrated that JQ1 significantly suppressed cellular proliferation and induced cell cycle arrest and apoptosis in ovarian cancer cells and mouse model via targeting c-Myc. In addition, JQ1 had multiple influences on cancer metabolism, particularly in the aerobic glycolysis pathway. JQ1 reduced both the activity and phosphorylation of LDHA, inhibited lactate production, and decreased the energy supply to ovarian cancer cell lines and tumors. Taken together, our findings suggest that JQ1 is an efficacious anti-tumor agent in ovarian cancer that is associated with cell cycle arrest, induction of apoptosis and alterations of metabolism.

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