脑源性神经营养因子对肝癌细胞氟尿嘧啶化疗敏感性的影响

Effect of brain-derived neurotrophic factor on chemosensitivity of hepatocellular carcinoma cells to fluorouracil

目的:探讨外源性脑源性神经营养因子(BDNF)对人肝癌Bel-7402细胞氟尿嘧啶(5-FU)化疗敏感性的影响。方法:分别用5-FU(5-FU组)和5-FU+BDNF(5-FU+BDNF组)处理Bel-7402细胞,以无干预的Bel-7402细胞作为对照组。用MTT法、克隆形成试验和流式细胞仪检测细胞生长与凋亡情况,RT-PCR法检测细胞bcl-2 mRNA的表达。结果:5-FU组细胞OD值、克隆形成数明显降低,细胞凋亡率明显升高,bcl-2 mRNA表达明显下调(均P<0.05),与对照组比较差异均有统计学意义(均P<0.05);而5-FU+BDNF组以上指标的改变均不明显,与对照组的差异均无统计学意义(均P>0.05)。结论:BDNF能降低肝癌Bel-7402细胞5-FU化疗敏感性,该作用可能与BDNF上调bcl-2的表达,从而抑制细胞凋亡有关。

Objective： To investigate the influence of brain-derived neurotrophic factor （BDNF） on the chemosensitivity of human hepatocellular carcinoma Bel-7402 cells to fl uorouracil （5-FU）. Methods： Bel-7402 cells were treated with 5-FU alone （5-FU group） or 5-FU plus BDNF （5-FU＋BDNF group） respectively, and the Bel-7402 cells without treatment served as control group. The cell growth and apoptosis were determined by MTT assay, colony formation assay, and flow cytometry respectively, and the bcl-2 mRNA expression in the cells was measured by RT-PCR method. Results： The OD value and number of colonies were significantly decreased, apoptosis rate was significantly increased, and bcl-2 mRNA expression was markedly down-regulated in the cells of 5-FU group, and all the differences had statistical significance compared with those of control group （all P＆lt;0.05）; the changes in all of the above variables in cells of 5-FU＋BDNF group were not evident, and the differences showed no statisticalsignificance compared with those of control group （all P＆gt;0.05）. Conclusion： BDNF can reduce the chemosensitivity of hepatocellular carcinoma Bel-7402 cells to 5-FU, and this eff ect may be associated with BDNF up-regulating the bcl-2 expression and thereby inhibiting cell apoptosis.