文献类型：期刊文献

英文题名：Enhancement of oxaliplatin sensitivity in human colorectal cancer by hypericin mediated photodynamic therapy via ROS-related mechanism

作者：Lin, Shengchao[1,2];Lei, Kecheng[1,2];Du, Wenpei[1,2];Yang, Liyan[1,2];Shi, Haiyang[1,2];Gao, Yuwei[1,2];Yin, Peihao[3];Liang, Xin[1,2];Liu, Jianwen[1,2]

机构：[1]E China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, POB 268,130 Meilong Rd, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, POB 268,130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Gen Surg, Shanghai 200062, Peoples R China

年份：2016

卷号：71

起止页码：24

外文期刊名：INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000369679800003)】；

基金：This work was supported by National Natural Science Foundation of China (No. 81502540), Fundamental Research Fund for the Central Universities of China (No. 222201514333), Shanghai Committee of Science and Technology (No. 13140902300), Shanghai Committee of Science and Technology (No. 13401900502), the Shanghai Committee of Science and Technology [grant 11DZ2260600].

语种：英文

外文关键词：Photodynamic therapy (PDT); Hypericin; Oxaliplatin; Nucleotide excision repair (NER); Glutathione; Glutathione S-transferase (GST)

摘要：The resistance to oxaliplatin (L-OHP) is a major obstacle to ideal therapeutic outcomes in colorectal cancer. Photodynamic therapy (PDT) induces tumor damage through photosensitizer-mediated oxidative cytotoxicity. Hypericin is a well-studied photosensitizer. In this study, we explored the role of hypericin-mediated PDT (HY-PDT) in sensitizing human colorectal cancer cells towards L-OHP. Pre-treatment with HY-PDT enhanced the anti-tumor activity of L-OHP via decreasing drug efflux and increasing platinum accumulation. Further research showed that HY-PDT-mediated resensitization of resistance cells towards L-OHP was dependent on regulation of MRP-2, instead of p-gp. HY-PDT was also found to inhibit intracellular glutathione (GSH) and Glutathione S-transferase (GST), suggesting the involvement of GSH-related detoxification in the sensitization effect. Additionally, enhanced DNA double-strand breaks (DSBs) was observed following HY-PDT/L-OHP combined treatment. HY-PDT lowered the removing rate of platinum from DNA and down-regulated the expression of ERCC1 and XPF, two critical enzymes involved in nucleotide excision repair (NER) pathway. GSH monoethyl ester (GSH-EE) antagonized HY-PDT-induced ROS and repressed sensitization to platinum. Taken together, HY-PDT mediated sensitization of L-OHP in human colorectal cancer is mediated by ROS, whose mechanism involves affecting drug efflux, GSH-related detoxification and NER-mediated DNA repair. (C) 2015 Elsevier Ltd. All rights reserved.