Effects of dihydroartemisinin on proliferation and apoptosis of human pancreatic cancer cell line

doi:10.16098/j.issn.0529-1356.2018.01.011

Abstract

Abstract:

Objective To investigate the effect of dihydroartemisinin on proliferation and apoptosis of human pancreatic cancer cell (PANC-1) and explore its mechanism.Methods After PANC-1cells treated with 30, 60, 120, 240 and 480 μmol/L dihydroartemisinin for 48 hours, MTT assay was used to detect the proliferation effect of dihydroartemisinin on PANC-1 cells. The cell cycle and apoptosis were detected by flow cytometry. The expressions of cyclin B1, Cdk1, p21 and apoptosis related protein Bcl-2, Bax, Caspase-3, Caspase-9 and cytochrome C(Cyto C) were detected by Western blotting. Results MTT result showed that the proliferation of PANC-1 cells was inhibited obviously after treatment with dihydroartemisinin by the concentration of 30-480 μmol/L (P<0.05). The result of flow cytometry showed that dihydroartemisinin could block PANC-1 cell cycle in G₂/M phase and induce cells apoptosis (P<0.05). The result of Western blotting showed that the expressions of Cdk1 and cyclin B1 were decreased and the expression of P21 increased after treatment with dihydroartemisinin. The expression of Bcl-2 was downregulated, expression of Bax was up-regulated, the ration of Bax/Bcl-2 was increased and the expression of cleaved Caspase-3, cleaved Caspase-9 and Cyto C were up-regulated. Conclusion Dihydroartemisinin can inhibit the proliferation of PANC-1 cells and induce apoptosis. The possible mechanism might be related to mitochondrial pathway.

Key words: Dihydroartemisinin, Pancreatic cancer, G₂/M block, Western blotting, Human

ZHU Wen-he XU Na XU Jun-jie ZHANG Hong LI Yan Lü Shi-jie ZHANG Wei. Effects of dihydroartemisinin on proliferation and apoptosis of human pancreatic cancer cell line[J]. Acta Anatomica Sinica, 2018, 49(1): 70-74.

References

［1］Lin QJ, Yang F, Jin C, et al. Current status and progress of pancreatic cancer in China ［J］. World J Gastroenterol, 2015, 21(26): 7988-8003.

［2］Xu Z, Pothula SP, Wilson JS, et al. Pancreatic cancer and its stroma: a conspiracy theory ［J］. World J Gastroenterol, 2014, 20(32): 11216-11229.

［3] Li F, Zhang W. Role of traditional Chinese medicine and its chemical components in anti-tumor metastasis ［J］. J Cancer Res Ther, 2014, 10 (Suppl): 120-126.

［4］Ling CQ, Yue XQ, Ling C. Three advantages of using traditional Chinese medicine to prevent and treat tumor ［J］. J Integr Med, 2014, 12(4): 331-335.

［5］Tao W, Luo X, Cui B, et al. Practice of traditional Chinese medicine for psycho-behavioral intervention improves quality of life in cancer patients: a systematic review and meta-analysis ［J］. Oncotarget, 2015, 6(37): 39725-39739.

［6］Lin R, Zhang Z, Chen L, et al. Dihydroartemisinin (DHA) induces ferroptosis and causes cell cycle arrest in head and neck carcinoma cells ［J］. Cancer Lett, 2016, 381(1): 165-175.

［7］Aung W, Sogawa C, Furukawa T, et al. Anticancer effect of dihydroartemisinin (DHA) in a pancreatic tumor model evaluated by conventional methods and optical imaging ［J］. Anticancer Res, 2011, 31(5): 1549-1558.

［8］Odaka Y, Xu B, Luo Y, et al. Dihydroartemisinin inhibits the mammalian target of rapamycin-mediated signaling pathways in tumor cells ［J］. Carcinogenesis, 2014, 35(1): 192-200.

［9］Lucibello M, Adanti S, Antelmi E, et al. Phospho-TCTP as a therapeutic target of Dihydroartemisinin for aggressive breast cancer cells ［J］. Oncotarget, 2015, 6(7): 5275-5291.

［10］Jia G, Kong R, Ma ZB, et al. The activation of c-Jun NH(2)-terminal kinase is required for dihydroartemisinin-induced autophagy in pancreatic cancer cells ［J］. J Exp Clin Cancer Res, 2014, 33:8.

［11］Li Y, Wang Y, Kong R, et al. Dihydroartemisinin suppresses pancreatic cancer cells via a microRNA-mRNA regulatory network ［J］. Oncotarget, 2016, 7(38): 62460-62473.

［12］Wu GS, Lu JJ, Guo JJ, et al. Synergistic anti-cancer activity of the combination of dihydroartemisinin and doxorubicin in breast cancer cells ［J］. Pharmacol Rep, 2013, 65(2): 453-459.

［13］Lee MH, Cho Y, Jung BC, et al. Parkin induces G2/M cell cycle arrest in TNF-alpha-treated HeLa cells ［J］. Biochem Biophys Res Commun, 2015, 464(1): 63-69.

［14］Yan Y, Hein AL, Greer PM, et al. A novel function of HER2/Neu in the activation of G2/M checkpoint in response to gammairradiation ［J］. Oncogene, 2015, 34(17): 2215-2226.

［15］Liu J, Ge YY, Zhu HC, et al. Fenofibrate increases radiosensitivity in head and neck squamous cell carcinoma via inducing G2/M arrest and apoptosis ［J］. Asian Pac J Cancer Prev, 2014, 15(16): 6649-6655.

［16］Xu XD, Yang L, Zheng LY, et al. Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses vasculogenic mimicry and proliferation of highly aggressive pancreatic cancer PaTu8988 cells ［J］. BMC Cancer, 2014, 14:373.

［17］Zhang H, Zhang T, Fang YSh, et al. Inhibitory effect of artemisinin combined with cisplatinon on HepG2 cells proliferation ［J］. Journal of Toxicology, 2016, (06): 435-440.（in Chinase）

张红, 张婷, 凡亚帅,等. 青蒿素联合顺铂抑制肝癌细胞HepG2增殖的影响［J］. 毒理学杂志, 2016, (06): 435-440.

［18］Chang C, Liu SP, Fang CH, et al. Effects of matrine on the proliferation of HT29 human colon cancer cells and its antitumor mechanism ［J］. Oncol Lett, 2013, 6(3): 699-704.

［19］Vaikundamoorthy R, Sundaramoorthy R, Krishnamoorthy V, et al. Marine steroid derived from acropora formosa enhances mitochondrial-mediated apoptosis in non-small cell lung cancer cells ［J］. Tumour Biol, 2016, 37(8): 10517-10531.

［20］Ling L, Yang P, Gai ShK, et al. Ginsenoside Rg1 inhibits apoptosis by inducing autophagy in Raw 264. 7 macrophages ［J］. Acta Anatomica Sinica, 2016, 47(5): 599-606.（in Chinase）

凌露, 杨萍, 盖盛坤,等. 人参皂苷Rg1通过自噬抑制Raw 2647巨噬细胞凋亡［J］. 解剖学报, 2016, 47(5): 599-606.

［21］Zhou ZH, Chen FX, Xu WR, et al. Enhancement effect of dihydroartemisinin on human gammadelta T cell proliferation and killing pancreatic cancer cells ［J］. Int Immunopharmacol, 2013, 17(3): 850-857.

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