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Small molecule BKM1972 inhibits human prostate cancer growth and overcomes docetaxel resistance in intraosseous models.

Abstract：

:Bone metastasis is a major cause of prostate cancer (PCa) mortality. Although docetaxel chemotherapy initially extends patients' survival, in most cases PCa becomes chemoresistant and eventually progresses without a cure. In this study, we developed a novel small-molecule compound BKM1972, which exhibited potent in vitro cytotoxicity in PCa and other cancer cells regardless of their differences in chemo-responsiveness. Mechanistic studies demonstrated that BKM1972 effectively inhibited the expression of anti-apoptotic protein survivin and membrane-bound efflux pump ATP binding cassette B 1 (ABCB1, p-glycoprotein), presumably via signal transducer and activator of transcription 3 (Stat3). BKM1972 was well tolerated in mice and as a monotherapy, significantly inhibited the intraosseous growth of chemosensitive and chemoresistant PCa cells. These results indicate that BKM1972 is a promising small-molecule lead to treat PCa bone metastasis and overcome docetaxel resistance.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Chen Y,Gera L,Zhang S,Li X,Yang Y,Mamouni K,Wu AY,Liu H,Kucuk O,Wu D

doi

10.1016/j.canlet.2019.01.010

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

62-72

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(19)30022-9

journal_volume

446

pub_type

杂志文章

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