KIB OpenIR
Isodon eriocalyx and its bioactive component Eriocalyxin B enhance cytotoxic and apoptotic effects of gemcitabine in pancreatic cancer
Li, L.; Zhao, S. L.; Yue, G. G. L.; Wong, T. P.; Pu, J. X.; Sun, H. D.; Fung, K. P.; Leung, P. C.; Han, Q. B.; Lau, C. B. S.; Leung, P. S.
2018
发表期刊PHYTOMEDICINE
ISSN0944-7113
卷号44页码:56-64
摘要Background: Pancreatic cancer, associated with poor prognosis and low survival rate, has been the fourth leading cause of cancer-related death in the US. Although gemcitabine (Gem) is the first-line chemotherapeutic drug in the management of pancreatic cancer, the median survival extension is only 1.5 months, indicating unsatisfactory clinical results. Therefore, exploring agents that can enhance the anti-cancer activity of Gem would be an attractive strategy. Purpose: Our previous studies have demonstrated that eriocalyxin b (EriB), an ent-kaurane diterpenoid isolated from Isodon eriocalyx (Dunn.) Hara, possesses anti-pancreatic cancer effects, thus acing as a potential therapeutic agent. In this study, we further investigated whether EriB or the ethanol extract of I. eriocalyx (Isodon) could potentiate the cytotoxic activity of Gem in human pancreatic adenocarcinoma cells. In addition, the mechanism associated with their effects was also studied. Methods: The anti-proliferation effect was assessed by MTT assay and Ki-67 immunostaining. The combination effect (addition, synergism and antagonism) of various agents was calculated by the Calcusyn software (Biosoft), utilizing the T.C. Chou Method. Apoptosis was detected using Annexin V and PI double staining followed by quantitative flow cytometry. Protein expression regulated by various treatments was analyzed by western blotting. Results: The combination index revealed that Gem and EriB (or Isodon extract) had synergistic anti-proliferative effect. Both cellular apoptotic and anti-proliferative effects of Gem were significantly increased after combination with EriB (or Isodon extract). The underlying mechanisms involved in the combination effects were elucidated, which include: (1) increased activation of the caspase cascade; (2) reduction of PDK1 and AKT phosphorylation; (3) induction of JNK phosphorylation by Isodon and Gem combination. Conclusion: Gem and EriB (or Isodon extract) taken together in combination regulated PDK1/AKT1/caspase and JNK signaling and promoted apoptosis synergistically, which may contribute to the much increased anti-proliferative activity compared to either agent alone.
收录类别SCI
语种英语
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/64740
专题中国科学院昆明植物研究所
推荐引用方式
GB/T 7714
Li, L.,Zhao, S. L.,Yue, G. G. L.,et al. Isodon eriocalyx and its bioactive component Eriocalyxin B enhance cytotoxic and apoptotic effects of gemcitabine in pancreatic cancer[J]. PHYTOMEDICINE,2018,44:56-64.
APA Li, L..,Zhao, S. L..,Yue, G. G. L..,Wong, T. P..,Pu, J. X..,...&Leung, P. S..(2018).Isodon eriocalyx and its bioactive component Eriocalyxin B enhance cytotoxic and apoptotic effects of gemcitabine in pancreatic cancer.PHYTOMEDICINE,44,56-64.
MLA Li, L.,et al."Isodon eriocalyx and its bioactive component Eriocalyxin B enhance cytotoxic and apoptotic effects of gemcitabine in pancreatic cancer".PHYTOMEDICINE 44(2018):56-64.
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