Sensitizing hormone-refractory prostate cancer cells to drug treatment by targeting 14-3-3sigma

Molecular Cancer Therapeutics
Baoguang HanJian-Ting Zhang

Abstract

Advanced and hormone-refractory prostate cancer has long been considered as a chemoresistant disease. Recently, it was found that 14-3-3sigma expression increases as prostate tumor progresses, and that 14-3-3sigma contributes significantly to drug resistance in breast cancers. We, thus, hypothesized that advanced and hormone-refractory prostate cancers may have an increased level of 14-3-3sigma, which in turn may contribute to drug resistance in advanced and hormone-refractory prostate cancers. In this study, we tested this hypothesis and found that, indeed, the expression level of 14-3-3sigma in androgen-independent prostate cancer cell lines DU145, PC3, and CWR22RV are much higher than that in the androgen-dependent cell line LNCaP, and that the androgen-independent cells are more resistant to mitoxantrone and Adriamycin than the androgen-dependent cells. Depleting 14-3-3sigma expression in DU145 and CWR22RV by RNA interference significantly sensitized these cells to mitoxantrone and Adriamycin by abrogating G2-M checkpoint and increasing apoptosis, whereas restoring 14-3-3sigma expression in LNCaP cells enhanced drug resistance. We also showed that 14-3-3sigma deficiency caused nuclear localization of Cdc2 and dephosphorylat...Continue Reading

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Citations

Feb 9, 2012·Breast Cancer Research and Treatment·Yukiko NakamuraShinzaburo Noguchi
Apr 22, 2009·Medical Oncology·Gaoming XiaoZhiqiang Xiao
Aug 30, 2011·Journal of Chemical Information and Modeling·Jing-Yuan LiuJian-Ting Zhang
Jan 16, 2013·Journal of Lipid Research·Hailan LiuJian-Ting Zhang
Nov 12, 2014·International Journal of Oncology·De-Yu ChenWen-Qing Qi
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Oct 16, 2009·The International Journal of Biochemistry & Cell Biology·Wei-Guo HuangZhi-Qiang Xiao
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Sep 18, 2013·The Journal of Biological Chemistry·Zhaomin LiJian-Ting Zhang
Jan 23, 2013·Cell Biology International·Vildan Bozok CetintasZuhal Eroglu
Jan 15, 2017·Molecular Cancer Research : MCR·Yifan ChenJian-Ting Zhang
Dec 9, 2020·Pharmaceuticals·Ghazi Aljabal, Beow Keat Yap
Sep 21, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yun HuangWeiguo Huang

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