Trillin can enhance the anti-cancer effect of fluorouracil on cervical cancer cells / 肿瘤

ABSTRACT

Objective: To investigate the enhancement effect of trillin on anti-cancer function of fluorouracil in cervical cancer cells. Methods: HeLa cells were treated with trillin (300 |xg/mL), fluorouracil (10 μg/mL), and fluorouracil (10 μg/mL) plus trillin (30, 100 and 300 |xg/mL), respectively. The inhibitory effects of trillin and fluorouracil on proliferation of HeLa cells were assayed by MTT method. Flow cytometry was applied to test the apoptosis of HeLa cells treated with trillin and fluorouracil. The expression levels of mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK), Akt and other proteins in apoptosis-related signaling pathways in Hela cells were determined by Western blotting. The xenograft tumor model of human HeLa cells in nude mice was established, and the anti-tumor effect of trillin in vivo was tested after intraperitoneal injection of trillin (300 mg/kg), fluorouracil (10 mg/kg), and fluorouracil (10 mg/kg) plus trillin (300 mg/kg), respectively. Results: As compared with treatment with fluorouracil alone, the combination of trillin and fluorouracil could improve the inhibitory effect on proliferation and apoptosis of HeLa cells (both P < 0.05). The tumor formation in nude mice administrated with trillin plus fluorouracil was inhibited, and this inhibitory effect was more significant than that in nude mice treated with fluorouracil alone (P < 0.05). The combination of trillin and fluorouracil inhibited the expressions of phosphorylated MEK/ERK and Akt proteins in HeLa cells, increased the activation of caspase-3 protein, down-regulated Bcl-2 expression, and up-regulated Bax expression. Conclusion: Trillin can enhance the anti-cancer function of fluorouracil on cervical cancer. It is suggested that trillin may be used as a potential chemosensitizer.