title: Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin.
abstract: Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. tjxuxiaodong@163.com.
authors.forename: Xiao Dong
authors.initials: XD
authors.lastname: Xu
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. zhaoy2401@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. zm0911work@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. heruizhi@aliyun.com.
authors.forename: Rui Zhi
authors.initials: RZ
authors.lastname: He
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 18771146878@163.com.
authors.forename: Xiu Hui
authors.initials: XH
authors.lastname: Shi
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. amjoyguo@126.com.
authors.forename: Xing Jun
authors.initials: XJ
authors.lastname: Guo
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. chengj1010@sina.com.
authors.forename: Cheng Jian
authors.initials: CJ
authors.lastname: Shi
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. nicholas.peng7@gmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. wangmin0013128@aliyun.com.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. shenming-2002@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. xwangtjh@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. kuai_1985@hotmail.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. ryqin@tjh.tjmu.edu.cn.
authors.forename: Ren Yi
authors.initials: RY
authors.lastname: Qin
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D015415:Biomarkers; D012402:Rotenone; D004317:Doxorubicin; C107676:deguelin
keywords: autophagy; deguelin; doxorubicin; pancreatic cancer