Pancreas · 2012
Triptolide cooperates with Cisplatin to induce apoptosis in gemcitabine-resistant pancreatic cancer.
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Zhu Wenbo, Li Jingjie, Wu Sihan, Li Shifeng, Le Liang, Su Xingwen, Qiu Pengxin, Hu Haiyan, Yan Guangmei
Аннотация
OBJECTIVES: 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.
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.
Предметные рубрики MeSH
AnimalsAntimetabolites, AntineoplasticAntineoplastic Agents, AlkylatingApoptosisCell Line, TumorCell SurvivalCisplatinDeoxycytidineDiterpenesDown-RegulationDrug Resistance, NeoplasmDrug SynergismEpoxy CompoundsFemaleHSP27 Heat-Shock ProteinsHumansMiceMice, NudeMitochondriaNeoplasm TransplantationPancreatic NeoplasmsPhenanthrenesRNA, Small InterferingTransfectionGemcitabine