期刊
BJU INTERNATIONAL
卷 111, 期 4, 页码 672-682出版社
WILEY
DOI: 10.1111/j.1464-410X.2012.11409.x
关键词
androgen-ablation therapy; autophagy; chemotherapy
资金
- Cancer Research UK
- MRC [G0900871] Funding Source: UKRI
- Cancer Research UK [15151, 15816] Funding Source: researchfish
- Medical Research Council [G0900871] Funding Source: researchfish
Objective To study the cellular effects of the anti-androgen bicalutamide on autophagy and its potential impact on response to androgen-ablation therapy (AAT) alone or combined with docetaxel chemotherapy in human prostate cancer LNCaP cells. Materials and Methods LNCaP cells were treated with bicalutamide +/- docetaxel, and cellular effects were assayed: lipidated LC3 (a microtubule-associated protein) for autophagy and its trafficking to fuse with lysosome; flow cytometry using propidium iodide or caspase 3 for cell death; and sulforhodamine B assay for cell growth. Results Bicalutamide treatment enhanced autophagy in LNCaP cells with increased level of autophagosome coupled with an altered cellular morphology reminiscent of neuroendocrine differentiation. Consistent with the literature on the interaction between androgen receptor activation and taxane chemotherapy, bicalutamide diminished docetaxel mediated cytotoxicity. Significantly, pharmacological inhibition of autophagy with 3-methyladenine significantly enhanced the efficacy cell kill mediated by AAT +/- docetaxel. Conclusion Autophagy associated with bicalutamide treatment in LNCaP cells may have a pro-survival effect and strategy to modulate autophagy may have a potential therapeutic value.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据