文献类型：期刊文献

英文题名：Hypericin-mediated photodynamic therapy enhances gemcitabine induced Capan-2 cell apoptosis via inhibiting NADPH level

作者：Sun, Liyun[1];Shang, Huoli[1];Wu, Yuzhen[1];Xin, Xiujuan[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Mei Long Rd, Shanghai 200237, Peoples R China

年份：2022

卷号：74

期号：4

起止页码：596

外文期刊名：JOURNAL OF PHARMACY AND PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000764419500001)】；

基金：This research was supported by The National Natural Science Fund (F100-41784) and Beijing Technology and Business University (The Open Research Fund Program of Key Laboratory of Cosmetic, CRS2020-02) and Technology and China Scholarship Council (File No. 201906745008).

语种：英文

外文关键词：hypericin; gemcitabine; Capan-2; apoptosis; reactive oxygen species

摘要：Objectives The combination of gemcitabine (Gem) and hypericin (HY) enhances the apoptosis of Capan-2 cells, providing a promising option for the treatment of pancreatic cancer. Our study further explored the cytotoxic mechanism of HY combined with chemotherapy drugs on pancreatic cancer. Methods The proliferation rate of the cells assayed with the MTT method. The ROS (reactive oxygen species) levels of each treatment were evaluated by DCFH-DA oxidisation methods. The activity of glutathione reductase and the levels of reduced glutathione (GSH) and oxidised glutathione (GSSG) were assessed using assay kits. The expression levels of apoptosis-related proteins were analysed by western blotting. Key findings The activity of glucose-6-phosphate dehydrogenase (G6PDH), a key enzyme of the pentose phosphate pathway, significantly decreased in Gem + HY groups, however, the ROS level enhanced accompanying with GSH depleting, mitochondrial membrane depolarisation and cytochrome C release. Gem + HY inhibits the expression of Bcl-2 but stimulates Bax level, triggering caspase activation and PARP cleavage and thus promoted apoptosis of Capan-2 cells. Conclusions We demonstrated that Gem combined HY-PDT could inhibit the proliferation of Capan-2 cells and induce cell apoptosis. HY-PDT combined with Gem had a great potential on pancreatic cancer treatment clinically.