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Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently shown anti-tumor activity in various cancer cells.However, its effect on pancreatic cancer is unknown, and the mechanism unclear.The study aims to investigate its antiturnor activity and underlying mechanisms in human pancreatic cancer BxPC-3 and AsPC-1 cells in vitro and subcutaneous BxPC-3 xenograft tumors in mice.MTT assay was used to evaluate cell viability, flow cytometry and laser scanning confocal microscopy, apoptosis, for cultured cells.Pancreatic tumors were established by subcutaneous injection of BxPC-3 cells in nude BALB/c mice, and DHA was i.p.administered to the mice.The size of tumors was monitored and harvested after the mice were sacrificed.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 expression of PCNA (proliferating cell nuclear antigen) and cyclin D1, and upregulated p21WAF1/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 DHA may be a potent and promising agent to combat pancreatic cancer.