期刊
ANTI-CANCER DRUGS
卷 20, 期 2, 页码 131-140出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0b013e3283212ade
关键词
apoptosis; dihydroartemisinin; pancreatic cancer; proliferation
资金
- Chinese Ministry of Education [NCET07-0248]
- Scientific Foundation for Excellent Youth in Heilongjiang Province, China [JC200717]
- National Natural Scientific Foundation of China [30571808, 30872987]
Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Its effect on pancreatic cancer is, however, unknown and the mechanism is unclear. The study aims to investigate its antitumor activity and underlying mechanisms in human pancreatic cancer BxPC-3 and AsPC-1 cells in vitro and subcutaneous BxPC-3 xenograft tumors in mice. The MTT assay was used to evaluate cell viability, and flow cytometry and laser scanning confocal microscopy were used to detect apoptosis, for cultured cells. Pancreatic tumors were established by subcutaneous injection of BxPC-3 cells In nude BALB/c mice, and DHA was administered intraperitoneally to the mice. The size of tumors was monitored and they were harvested after the mice had been killed. Tumor sections were immunostained with an anti-Ki-67 Ab to assess the proliferation index, or stained with TUNEL to evaluate in-situ cell apoptosis. The gene expression in cells and tumors was evaluated by western blot analysis. In the cultured cells, DHA Inhibited cell viability, downregulated the expression of proliferating cell nuclear antigen and cyclin D1, and upregulated p21(WAF1/CIP1); and induced apoptosis by reducing the ratio of Bcl-2/Bax and increasing the activation of caspase-9, in a dose-dependent manner, Similarly, in mice bearing BxPC-3 xenograft tumors, administration of DHA inhibited tumor growth in a dose-dependent manner, and modulated tumoral gene expression consistent with the in-vitro observations. This study indicates that DHA may be a potent and promising agent to combat pancreatic cancer. Anti-Cancer Drugs 20:131-140 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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