Autophagy protects LNCaP cells under androgen deprivation conditions
Autophagy protects LNCaP cells under androgen deprivation conditions
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自噬在雄激素剥夺条件下保护 LNCaP 细胞
DOI：
10.4161/auto.5209
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发表时间：
2008-01-01
期刊：
影响因子：
13.3
通讯作者：
Xi, Zhijun
中科院分区：
文献类型：
--
作者：
Li, Mengqiang;Jiang, Xuejun;Xi, Zhijun
雄激素在前列腺癌的发生发展中起关键作用。然而，雄激素在自噬过程中的调节作用以及雄激素剥夺后增加的自噬小体的功能仍然知之甚少。我们发现，去血清诱导的LNCaP细胞自噬小体可被双氢睾酮(DHT)显著抑制。3-甲基腺嘌呤抑制自噬的药理作用使无血清培养的LNCaP细胞较含DHT或血清培养的LNCaP细胞凋亡增加。此外，去除Beclin 1以抑制小干扰RNA的自噬，会导致LNCaP细胞在无血清的培养液中的增殖速度慢于在有DHT的培养液中。综上所述，这些发现表明LNCaP细胞可以在雄激素剥夺条件下通过自噬途径存活，这可能是前列腺癌细胞从雄激素依赖细胞向雄激素非依赖细胞转变的一种新机制。
Androgen plays a critical role in the development and progression of prostate cancer. However, the regulatory role of androgen in the autophagic process and the function of the increased autophagosomes following androgen deprivation remain poorly understood. We found that autophagosomes, which were induced upon serum deprivation in LNCaP cells, can be significantly suppressed by dihydrotestosterone (DHT). Pharmacological inhibition of autophagy by 3-methyladenine led to increased apoptosis of LNCaP cells in serum-free medium compared to the medium with DHT or serum. Additionally, depletion of Beclin 1 to inhibit autophagy by small interfering RNA resulted in a slower proliferation of LNCaP cells in the medium depleted of serum than in the medium with DHT. Altogether, these findings suggested that LNCaP cells can resort to the autophagic pathway to survive under androgen deprivation conditions, which can be a novel mechanism involved in the transition of prostate cancer cells from an androgen-dependent to an androgen-independent cell type.