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Phloretin (Ph), which is obtained from apples, juice, and cider, is a known inhibitor of the type Ⅱ glucose transporter (GLUT2).In this study, elevated expression (> 5-fold) of GLUT2 mRNA was detected by real-time PCR analysis of laser-capture microdissected (LCM) human hepatoma cells when compared to non-malignant hepatocytes.Here, we performed in vitro and in vivo studies of the anti-tumor activity of Ph in combined treatment of human liver cancer cells with paelitaxel (PTX).Inhibition of GLUT2 by Ph potentiated the anticancer effects of PTX, which allowed human liver cancer cells to overcome drug resistance.Our results demonstrate that Ph (50-150 μM) significantly potentiates PTX (10 nM)-induced DNA laddering formation in Hep G2 cells.Caspases 3, 8 and 9 were involved in the apoptosis, as evidenced by activity assays.The antitumor therapeutic efficacy of Ph (10 mg/Kg body weight) was determined by combined treatment of cells with PTX (1 mg/Kg body weight) in the SCID mouse model.The Hep G2-xenografted tumor volume was reduced significantly (> 5-fold) in the Ph+PTX-treated mice when compared to the PTX-treated group.These results suggest that Ph may be useful for cancer chemotherapeutic and chemopreventive purposes.