Postdoctoral Research Station, General Hospital of Central Theater Command, Wuhan, Hubei 430070, China; Department of Gastroenterology, General Hospital of Central Theater Command, Wuhan, Hubei 430070, China; School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, China.
Department of Gastroenterology, General Hospital of Central Theater Command, Wuhan, Hubei 430070, China; School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, China.
Photodiagnosis Photodyn Ther. 2024 Oct;49:104319. doi: 10.1016/j.pdpdt.2024.104319. Epub 2024 Aug 22.
Photodynamic therapy (PDT) is a promising and innovative approach for treating tumors. The synergistic effect of PDT and chemotherapy can enhance the anti-tumor efficacy by leveraging their complementing benefits. In this study, we created lipid vesicles to deliver a photosensitizer (chlorin e6, Ce6) and Regorafenib into tumors for the purpose of examining the effectiveness and mechanism of Lipo-Ce6@Rego-PDT (LCR-P) on Hepatocellular carcinoma (HCC) both in vitro and in vivo. We found that the cytotoxicity on HCC caused by LCR-P was significantly stronger than that caused by Lipo-Ce6-PDT (LC-P). Cellular ROS production in the LCR-P group was approximately higher than that in the LC-P group, and Regorafenib significantly inhibited the phosphorylation of JNK, ERK, and P38 of Lipo-Ce6-PDT group in vitro and in vivo. Furthermore, Regorafenib significantly downregulated the expression of Bcl-2 and upregulated the expression of Bax and cleaved caspase-3 of LC-P group in vitro and in vivo. Compared with LC-P, LCR-P significantly increased cell apoptosis rate. The body weight and HE staining of normal organs primarily indicated the safety of this combined strategy. These results indicate that the combination of Regorafenib and Lipo-Ce6 can significantly enhance the anti-tumor efficiency of PDT for HCC and exhibits good biosafety.
光动力疗法（PDT）是一种有前途的创新方法，可用于治疗肿瘤。PDT 和化疗的协同作用可以通过利用它们的互补优势来增强抗肿瘤疗效。在这项研究中，我们创建了脂质体来将光敏剂（氯乙酮 6，Ce6）和瑞戈非尼递送到肿瘤中，以研究 Lipo-Ce6@Rego-PDT（LCR-P）对肝癌（HCC）的体内外疗效和机制。我们发现，LCR-P 对 HCC 的细胞毒性明显强于 Lipo-Ce6-PDT（LC-P）。LCR-P 组的细胞内 ROS 产生量明显高于 LC-P 组，并且在体外和体内，瑞戈非尼显著抑制了 Lipo-Ce6-PDT 组 JNK、ERK 和 P38 的磷酸化。此外，瑞戈非尼在体外和体内均显著下调了 LC-P 组 Bcl-2 的表达，上调了 Bax 和 cleaved caspase-3 的表达。与 LC-P 相比，LCR-P 显著增加了细胞凋亡率。正常器官的体重和 HE 染色主要表明了这种联合策略的安全性。这些结果表明，瑞戈非尼和 Lipo-Ce6 的联合可以显著增强 PDT 对 HCC 的抗肿瘤效率，并表现出良好的生物安全性。
