title: Triptolide cooperates with Cisplatin to induce apoptosis in gemcitabine-resistant pancreatic cancer.
abstract: OBJECTIVE
  We aim to pharmacologically downregulate heat shock protein 27 (HSP27) through triptolide (TPL) to improve the drug sensitivity of pancreatic cancer to cisplatin (DDP).
  
  
  METHODS
  In vitro, we assessed cell viability and apoptosis by the combination of TPL and DDP in gemcitabine-resistant human pancreatic carcinoma PANC-1 and MIA PaCa-2 cell lines and examined the effect of silencing HSP27 by a small interfering RNA on cytotoxicity induced by TPL or DDP. In vivo, we apply TPL with DDP in a xenograft model to test the synergic action.
  
  
  RESULTS
  Triptolide cooperates with DDP to decrease cell viability and to induce apoptosis via the mitochondrial pathway, which is accompanied by a sharp decline in HSP27. Knocking down endogenous HSP27 can sensitize cancer cells to cytotoxicity with TPL or DDP, indicating the critical role of HSP27 down-regulation in the synergic effect. Meanwhile, TPL acts in synergy with DDP to cause tumor regression in vivo.
  
  
  CONCLUSIONS
  The combined therapy of TPL and DDP triggers a synergic apoptosis via inhibiting HSP27 in human gemcitabine-resistant pancreatic carcinoma and has a strong potential to be developed into a new effective regimen for pancreatic cancer treatment.
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhu
authors.forename: Jingjie
authors.initials: J
authors.lastname: Li
authors.forename: Sihan
authors.initials: S
authors.lastname: Wu
authors.forename: Shifeng
authors.initials: S
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Le
authors.forename: Xingwen
authors.initials: X
authors.lastname: Su
authors.forename: Pengxin
authors.initials: P
authors.lastname: Qiu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
authors.forename: Guangmei
authors.initials: G
authors.lastname: Yan
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000031:analogs & derivatives*; D004224:Diterpenes / Q000008:administration & dosage*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004852:Epoxy Compounds / Q000008:administration & dosage; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000502:physiology; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010616:Phenanthrenes / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D055551:HSP27 Heat-Shock Proteins; D010616:Phenanthrenes; D034741:RNA, Small Interfering; D003841:Deoxycytidine; C001899:triptolide; D002945:Cisplatin; D000093542:Gemcitabine