The inhibitory effect of artesunate on human esophageal carcinoma is associated with modulation of CDC25A and TGFβ / 肿瘤

ABSTRACT

Objective: To observe the effects of artesunate (Art) on the proliferation of human esophageal carcinoma Eca109 cell line and xenograft tumors in nude mice, and explore the relationship between Art-induced cell cycle arrest and the expressions of CDC25A and transforming growth factor beta (TGFβ). Methods: The inhibitory effect of Art on proliferation of human esophageal carcinoma Eca109 cells and normal human peripheral blood mononuclear cells (hPBMC) at different concentrations were determined by MTT assay. The changes of cell cycle distribution of tumor cells were determined by flow cytometry (FCM). The inhibitory effects of Art on the growth of transplanted human esophageal carcinoma in nude mice was observed. The expression of CDC25A mRNA was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein expressions of CDC25A and TGFβ were measured by Western blotting. Results: Art significantly inhibited the proliferation of Eca109 cells with the IC50, of (68.80 ± 0.76) μmol/L. However it had no apparent effect on the proliferation of hPBMC. Art at low concentrations arrested the Eca109 cells at G0/G1 phase and significantly decreased the number of cells in S phase. Art at 100 μmol/L arrested Eca109 cells at G2/M phase. The volume and weight of xenograft tumors significantly were decreased in Art-treated group compared with model group. The maximal inhibitory ratio was 76.4% for tumor volume and 63.2% for tumor weight, respertively. Art dramatically inhibited mRNA and protein expression of CDC25A, while upregulated the expression of TGFβprotein. Conclusion: Art inhibits the proliferation of tumor cells with no apparent side effects. Art exerts its anti-tumor effect via modulating cell cycle distribution by upregulation of TGFβ and downregulation of CDC25A expression.