文献类型：期刊文献

英文题名：Berberine-photodynamic therapy sensitizes melanoma cells to cisplatin-induced apoptosis through ROS-mediated P38 MAPK pathways

作者：Wang, Xiaotong[1,2];Gong, Qianyi[1,2];Song, Changfeng[1,2];Fang, Jiaping[1,2];Yang, Yun[3];Liang, Xin[1,2];Huang, Xuan[3,4,5];Liu, Jianwen[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[3]Jiaxing Univ, Sch Med, Dept Pharm, Jiaxing 314001, Zhejiang, Peoples R China;[4]Nat Med & Hlth Food Res & Technol Innovat Team Ji, Jiaxing 314001, Zhejiang, Peoples R China;[5]Jiaxing Key Lab Oncol Photodynam Therapy & Target, Jiaxing, Peoples R China

年份：2021

卷号：418

外文期刊名：TOXICOLOGY AND APPLIED PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000639281700002)】；

基金：This work was supported by the National Natural Science Foundation of China (No. 81873050). The Jiaxing Key Laboratory of Tumor Photodynamic Therapy and Targeted Drug Research also provided financial supports for our research.

语种：英文

外文关键词：Photodynamic therapy (PDT); Berberine; Cisplatin; Melanoma cancer; ROS

摘要：The clinical use of cisplatin are limited due to its drug resistance. Thus, it is urgent to find effective combination therapy that sensitizes tumor cells to this drug. The combined chemo-photodynamic therapy could increase antitumor efficacy while also reduce the side effects of cisplatin. Berberine is an isoquinoline alkaloid, which has been reported to show high photosensitizing activity. In this study, we have examined the effect of a combination of cisplatin and berberine-PDT in cisplatinresistant melanoma cells. The cytotoxic effects of berberine-PDT alone or in combination with cisplatin were tested by MTT assays. We then examined the subcellular localization of berberine with confocal fluorescence microscopy. The percentage of apoptotic cells, the mitochondrial membrane potential (??m) and reactive oxygen species (ROS) generation assessed using flow cytometry analysis. Western blotting used in this study to determine the expression levels of MAPK signaling pathways and apoptosis-related proteins. Experimental data revealed that the mode of cell death is the caspase-dependent mitochondrial apoptotic pathways. Excessive accumulation of ROS played a key role in this process, which is confirmed by alleviation of cytotoxicity upon pretreatment with NAC. Furthermore, we found that the combined treatment activated MAPK signaling pathway. The inhibition of p38 MAPK by pretreating with SB203580 block the combined treatment-induced apoptotic cell death. In conclusion, berberine-PDT could be used as a chemo-sensitizer by promoting cell death through activation of a ROS/p38/caspase cascade.