癌细胞自噬机制
自噬( autopaghy) 是捕获和降解溶酶体中受损蛋白和细胞器的分解代谢过程,能有效降解正常细胞代谢产物,是维持机体健康的基础。营养缺乏、缺氧、DNA 损伤和细胞毒作用等均可以诱导细胞自噬发生。诱导自噬可通过调整细胞内外的动态平衡而促进细胞存活,然而过度的自噬则严重影响胚胎分化诱导细胞程序性死亡。因此,自噬的改变与临床各种疾病如癌症、神经退行性变、心脏疾病、肝和代谢紊乱、传染病、炎症和自身免疫性疾病等密切相关。过去的十年中,自噬作为一种新的方法在疾病治疗中受到了广泛的关注。
然而
,
目前尚未发现临床可行的干预措施
。
唯一在体内有效且在临床试验中安全的自噬抑制剂是氯喹及其衍生物羟氯喹(
Hydroxychloroquine
,
HCQ
) ,它们通过阻断自噬体融合和降解抑制自噬。
涉及或HCQ 的
30
多个
I/II
期癌症临床试验提示自噬抑制剂与抗肿瘤活性有关
。
因此
,
明确自噬如何调节细胞代谢为肿瘤生长提供营养物质是癌症治疗的关键点。
【
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