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.

中文翻译：

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光热暴露后自噬的抑制促进细胞凋亡并抑制肝细胞癌的生长。

光热疗法（PTT）是一种新近开发的有前途的策略，用于治疗肝细胞癌（HCC）。然而，迄今为止，已经广泛研究了凋亡作为PTT对癌症潜在作用的机制。在这里，我们探讨了这些治疗作用的替代机制，包括在温和温度下的凋亡以及PTT期间细胞周期阻滞和自噬的激活。我们使用808nm激光，用聚多巴胺（PDA）涂层的支链Au-Ag纳米颗粒以不同浓度与PTT一起处理了HCC细胞系HepG2。基于流式细胞术，凋亡相关蛋白（BAX，BCL2，胱天蛋白酶3）的Western印迹分析，Hoechst染色和TUNEL染色评估凋亡。要探索自噬的作用，我们用自噬抑制剂氯喹二磷酸处理细胞。自噬被抑制后，观察到纳米粒子处理增强了PTT诱导的细胞凋亡。此外，自噬的抑制作用显着增强了对肿瘤生长的抑制作用在HepG2小鼠异种移植模型中进行体内实验。这些结果表明，进一步探索PTT的机制可以帮助指导其临床应用，并且自噬抑制与PTT结合可能是HCC治疗的有希望的策略。