title: Endoplasmic reticulum stress and autophagy participate in apoptosis induced by bortezomib in cervical cancer cells.
abstract: OBJECTIVE
  To determine the role of endoplasmic reticulum (ER) stress and autophagy in apoptosis induced by bortezomib in human cervical cancer-derived HeLa cells and CaSki cells.
  
  
  RESULTS
  Bortezomib treatment activated apoptosis, evidenced by increased expression of cleaved caspase-3 and cleaved PARP in both HeLa cells and CaSki cells. Bortezomib also induced the loss of the mitochondrial membrane potential, increased the level of ER stress-associated proteins GRP78, ATF4, and CCAAT-enhancer-binding protein homologous protein, and affected the expression of autophagy-related proteins; increasing the levels of LC3-II and ATG5-ATG12 and decreasing the level of p62. When we combined bortezomib with the ER stress activator tunicamycin, or autophagy inhibitors 3-methyladenine or chloroquine, cell growth inhibition and apoptosis were markedly enhanced.
  
  
  CONCLUSIONS
  Bortezomib activates apoptosis signaling, and activation of ER stress and inhibition of autophagy enhances the cytotoxicity of bortezomib, suggesting that these combination treatments may be potential chemotherapy strategies for treating cervical cancer.
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 10026, China. 431097284@qq.com.
authors.forename: Yudi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Gynecological Department, Maternal and Child Health Hospital of Shanxi Province, Xi'an, 710003, Shanxi, China. 1007866405@qq.com.
authors.forename: Changmin
authors.initials: C
authors.lastname: Bai
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 10026, China. yinghua1168@163.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 10026, China. zhaodongxucc@126.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 10026, China. binzhangccc@126.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Gao
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 10026, China. zhangweiyuan1168@163.com.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001343:Autophagy; D000069286:Bortezomib / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D000069286:Bortezomib
keywords: Autophagy; Bortezomib; Cervical cancer; Endoplasmic reticulum stress