自噬通过脂滴降解调节雄激素敏感前列腺癌细胞的脂肪分解和细胞存活。
Autophagy regulates lipolysis and cell survival through lipid droplet degradation in androgen-sensitive prostate cancer cells.
机构信息
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
出版信息
Prostate. 2012 Sep 15;72(13):1412-22. doi: 10.1002/pros.22489. Epub 2012 Jan 31.
BACKGROUND
Androgen deprivation therapy, one of the standard treatments for prostate cancer (PCa) induces apoptosis, as well as autophagy in androgen-responsive PCa cells. As autophagy can promote either cell survival or death, it is important to understand its role in PCa treatment. The objective of this study was to elucidate the function of autophagy in lipid droplet (LD) homeostasis and survival in androgen-sensitive PCa cells.
METHODS
To produce androgen deprivation, charcoal filtered serum or the androgen inhibitor casodex were used in LNCaP and LAPC4 cells. Autophagy was monitored by immunofluorescence/confocal microscopy and immunoblot analysis. Levels of intracellular LDs and triacyglycerols after the inhibition of autophagy by 3-methyladenine, bafilomycin A(1) , or si-ATG5 were quantified by three independent methods, Oil Red O staining, triacyglycerols lipase assay, and nuclear magnetic resonance.
RESULTS
Androgen deprivation induced autophagy and the depletion of LDs in both of the androgen-sensitive PCa cell lines examined, whereas the blockage of autophagy by pharmacological or genetic means inhibited LD degradation and therefore lipolysis and cell growth. In addition, under androgen deprivation, increased colocalization of LDs and autophagic vesicles was observed in LNCaP cells, which can be further enhanced by blocking the autophagic flux.
CONCLUSION
Autophagy mediates LD degradation and lipolysis in androgen-sensitive PCa cells during androgen deprivation which aids the survival of PCa cells during hormone therapy.
背景
雄激素剥夺疗法是前列腺癌（PCa）的标准治疗方法之一，它可诱导雄激素反应性 PCa 细胞凋亡和自噬。由于自噬既可以促进细胞存活，也可以促进细胞死亡，因此了解其在 PCa 治疗中的作用非常重要。本研究旨在阐明自噬在雄激素敏感型 PCa 细胞中脂滴（LD）稳态和存活中的作用。
方法
采用活性炭过滤血清或雄激素抑制剂 casodex 使 LNCaP 和 LAPC4 细胞发生雄激素剥夺。通过免疫荧光/共聚焦显微镜和免疫印迹分析监测自噬。用 3-甲基腺嘌呤、巴弗洛霉素 A(1)或 si-ATG5 抑制自噬后，通过三种独立的方法（油红 O 染色、三酰基甘油脂肪酶测定和核磁共振）定量测定细胞内 LD 和三酰基甘油的水平。
结果
雄激素剥夺诱导了两种雄激素敏感型 PCa 细胞系中的自噬和 LD 耗竭，而用药理学或遗传学方法阻断自噬则抑制了 LD 降解，从而抑制了脂解和细胞生长。此外，在雄激素剥夺下，LNCaP 细胞中观察到 LD 与自噬小泡的共定位增加，而阻断自噬流可以进一步增强这种共定位。
结论
自噬介导了雄激素敏感型 PCa 细胞在雄激素剥夺期间的 LD 降解和脂解，这有助于 PCa 细胞在激素治疗期间的存活。
Zotero 插件