阿朴戈斯泊酮，一种新型抗凋亡 Bcl-2 家族蛋白抑制剂，能够诱导 PC-3 和 LNCaP 前列腺癌细胞发生自噬。
Apogossypolone, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces autophagy of PC-3 and LNCaP prostate cancer cells in vitro.
机构信息
Department of Blood Transfusion, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
出版信息
Asian J Androl. 2010 Sep;12(5):697-708. doi: 10.1038/aja.2010.57. Epub 2010 Jul 26.
Abstract
Limited treatment options are available for aggressive prostate cancer. Gossypol has been reported to have a potent anticancer activity in many types of cancer. It can increase the sensitivity of cancer cells to alkylating agents, diminish multidrug resistance and decrease metastasis. Whether or not it can induce autophagy in cancer cells has not yet been determined. Here we investigated the antiproliferative activity of apogossypolone (ApoG2) and (-)-gossypol on the human prostate cancer cell line PC3 and LNCaP in vitro. Exposure of PC-3 and LNCaP cells to ApoG2 resulted in several specific features characteristic of autophagy, including the appearance of membranous vacuoles in the cytoplasm and formation of acidic vesicular organelles. Expression of autophagy-associated LC3-II and beclin-1 increased in both cell lines after treatment. Inhibition of autophagy with 3-methyladenine promoted apoptosis of both cell types. Taken together, these data demonstrated that induction of autophagy could represent a defense mechanism against apoptosis in human prostate cancer cells.
摘要
对于侵袭性前列腺癌，治疗选择有限。己烯雌酚已被报道在多种类型的癌症中具有很强的抗癌活性。它可以增加癌细胞对烷化剂的敏感性，减少多药耐药性并降低转移。它是否能诱导癌细胞自噬尚未确定。在这里，我们研究了脱棉子酚（ApoG2）和（-）-棉酚对体外人前列腺癌细胞系 PC3 和 LNCaP 的增殖活性。ApoG2 暴露于 PC-3 和 LNCaP 细胞导致自噬的几个特征，包括细胞质中出现膜性空泡和酸性囊泡细胞器的形成。自噬相关 LC3-II 和 beclin-1 的表达在两种细胞系中均增加。用 3-甲基腺嘌呤抑制自噬可促进两种细胞类型的凋亡。综上所述，这些数据表明，自噬的诱导可能代表人类前列腺癌细胞中对抗细胞凋亡的防御机制。
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