文献类型：期刊文献

英文题名：Endoplasmic reticulum-targeting photosensitizer Hypericin confers chemosensitization towards oxaliplatin through inducing pro-death autophagy

作者：Lin, Shengchao[1,2];Yang, Liyan[1,2];Shi, Haiyang[1,2];Du, Wenpei[1,2];Qi, Yingxue[1,2];Qiu, Cen[1,2];Liang, Xin[1,2];Shi, Weibin[3];Liu, Jianwen[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Sch Pharm, POB 268,130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, POB 268,130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Shanghai Jiao Tong Univ, Dept Gen Surg, Xinhua Hosp, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China

年份：2017

卷号：87

起止页码：54

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

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000403528400008)】；

基金：We are grateful to Prof. Feng Qian (Fudan University, Shanghai China) for providing the pCDNA3.1-GFP-LC3 plasmid. This work was supported by Shanghai Committee of Science and Technology [grant 11DZ2260600] and Program of Shanghai Health and Family Planning Commission (201440495).

语种：英文

外文关键词：Endoplasmic reticulum (ER); Photodynamic therapy (PDT); Autophagic cell death; Chemo-sensitization

摘要：Hypericin is an endoplasmic reticulum (ER)-located photosensitizer, which causes oxidative damage to ER during photodynamic therapy (PDT). Hypericin-mediated PDT (HY-PDT) has been confirmed to enhance chemosensitivity of oxaliplatin (L-OHP) in colon cancer cells. The present study reveals that autophagy plays a key role in chemosensitization during HY-PDT. We proved pro-death autophagy was required for sensitization and HY-PDT/L-OHP antitumor synergism. High dosage of HY-PDT induced autophagic cell death; while low dose of HY-PDT predominantly triggered protective autophagy and promoted cell proliferation. Low dose of HY-PDT reduced the cytotoxicity of L-OHP in oxaliplatin-resistant colon cancer cells. Different level of autophagy therefore contributed to the opposite effect of HY-PDT on cell fate and chemo-sensitivity. Furthermore, we revealed the role of CHOP as a regulator connecting pro-survival and pro-death autophagy under ER damage. High dose of HY-PDT induced massive ROS generation and severe ER stress, which then led to induction of CHOP. CHOP thereby activated CHOP/TRIB3/Akt/mTOR cascade and triggered autophagic cell death. Additionally, when apoptotic pathway was blocked, cells treated with high dose of HY-PDT preferentially underwent death through autophagic pathway. On the other hand, suppression of autophagy made cells more vulnerable to apoptosis under low dose of HY-PDT. These results provided new evidences for the clinical application of ER-targeting PDT in modifying chemosensitivity of colorectal cancer therapy.