Inhibition of Autophagy Promoted Apoptosis and Suppressed Growth of Hepatocellular Carcinoma Upon Photothermal Exposure
Inhibition of Autophagy Promoted Apoptosis and Suppressed Growth of Hepatocellular Carcinoma Upon Photothermal Exposure
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光热照射下自噬的抑制促进细胞凋亡并抑制肝细胞癌的生长
DOI：
10.1166/jbn.2019.2714
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发表时间：
2019
影响因子：
2.9
通讯作者：
Jiang Jinlan
中科院分区：
文献类型：
--
作者：
Wang Yuqian;Zhao Hong;Wang Dezhou;Hao Miao;Kong Chenfei;Zhao Xiaoming;Gao Yiyao;Li Jing;Liu Baocai;Yang Bai;Zhang Hao;Jiang Jinlan
光热疗法（PTT）是近年来发展起来的一种治疗肝细胞癌（HCC）的有效方法。然而，迄今为止，细胞凋亡已被广泛研究为PTT对癌症的潜在作用机制。在这里，我们探讨了这些治疗效果的替代机制，包括除了在温和温度下的细胞凋亡之外，PTT期间细胞周期停滞和自噬的激活。我们使用808 nm激光，用不同浓度的聚多巴胺（PDA）涂覆的分支Au-Ag纳米颗粒与PTT一起处理HCC细胞系HepG 2。采用流式细胞术、凋亡相关蛋白（BAX、BCL 2、caspase 3）的蛋白质印迹分析、Hoechst染色和TUNEL染色评价细胞凋亡。为了探索自噬的作用，我们用自噬抑制剂二磷酸氯喹处理细胞。在自噬被抑制后，观察到通过PTT与纳米颗粒处理的凋亡增强。此外，在HepG 2小鼠异种移植模型中，自噬的抑制显著增强了对体内肿瘤生长的抑制。这些结果提示，进一步探讨PTT的作用机制有助于指导其临床应用，自噬抑制联合PTT治疗肝癌有望成为一种新的治疗策略。
Photothermal therapy (PTT) is a recently developed and promising strategy for the treatment of hepatocellular carcinoma (HCC). However, apoptosis has been extensively investigated as the mechanism of the underlying effect of PTT on cancer to date. Here, we explored alternative mechanisms of these therapeutic effects, including the activation of cell-cycle arrest and autophagy during PTT in addition to apoptosis under mild temperature. We treated the HCC cell line HepG2 with polydopamine (PDA)-coated branched Au–Ag nanoparticles at various concentrations along with PTT using an 808-nm laser. Apoptosis was evaluated based on flow cytometry, western blot analysis of apoptosis related proteins (BAX, BCL2, caspase 3), Hoechst staining, and TUNEL staining. To explore the role of autophagy, we treated cells with the autophagy inhibitor chloroquine diphosphate. Enhancement of apoptosis by PTT with nanoparticle treatment was observed after autophagy was inhibited. Moreover, inhibition of autophagy markedly enhance the suppression of tumor growth in vivo in a HepG2 mouse xenograft model. These results suggest that further exploration of the mechanism of PTT can help guide its clinical application, and that autophagy inhibition combined with PTT could be a promising strategy for HCC treatment.