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目的探讨三苯氧胺(tamoxifen,TAM)联合5-氟尿嘧啶(5-FU)对人结肠癌细胞株HT-29的增殖、凋亡及细胞迁移的影响。方法采用MTT法、流式细胞仪分别检测不同浓度(12.5、25、50μmol/L)5-FU及其联合TAM对HT-29细胞增殖的抑制作用、细胞凋亡的诱导作用,应用细胞划痕实验检测TAM(1×10-7、1×10-6、1×10-5、1×10-4mol/L)、5-FU及其联合TAM对细胞迁移的抑制作用。结果 5-FU及其联合TAM均可提高HT-29细胞增殖抑制率,单用5-FU的抑制率分别为(50.8±8.9)%和(62.8±8.8)%和(69.7±9)%,12.5μmol/L 5-FU联合低浓度TAM(1×10-7、1×10-6 mol/L)的抑制率分别为(82.9±2.9)%和(84.0±1.6)%,其作用呈剂量依赖关系;高浓度(1×10-4mol/L)TAM联合12.5μmol/L 5-FU表现出明显的促细胞凋亡作用[凋亡率为(95.7±4.2)%];划痕实验证实经1×10-6和1×10-5mol/L TAM及单用5-FU处理HT-29细胞72 h后均可明显地抑制细胞的迁移,但联合用药未显示出较TAM单药更明显的抑制作用。结论 TAM和5-FU均具有抑制细胞增殖、迁移和促进细胞凋亡的作用,TAM亦可增加结肠癌细胞株HT-29对5-FU的敏感性。
Objective To investigate the effects of tamoxifen (TAM) combined with 5-fluorouracil (5-FU) on the proliferation, apoptosis and cell migration of human colon cancer cell line HT-29. Methods MTT assay and flow cytometry were used to detect the inhibitory effects of different concentration (12.5, 25, 50μmol / L) 5-FU and its combined TAM on the proliferation of HT-29 cells and the induction of apoptosis. The inhibitory effect of TAM (1 × 10-7, 1 × 10-6, 1 × 10-5, 1 × 10-4mol / L), 5-FU and TAM on cell migration was tested. Results Both 5-FU combined with TAM increased the inhibitory rate of HT-29 cell proliferation. The inhibitory rates of 5-FU alone and 5-FU alone were (62.8 ± 8.8)% and (69.7 ± 9)%, The inhibitory rates of 12.5μmol / L 5-FU combined with low concentration of TAM (1 × 10-7,1 × 10-6 mol / L) were (82.9 ± 2.9)% and (84.0 ± 1.6)%, respectively, (1 × 10-4mol / L) TAM combined with 12.5μmol / L 5-FU showed obvious pro-apoptotic effects [apoptosis rate (95.7 ± 4.2)%]; scratch test confirmed that HT-29 cells treated with 1 × 10-6 and 1 × 10-5mol / L TAM and 5-FU alone could significantly inhibit the migration of HT-29 cells, but the combination therapy did not show more obvious than TAM alone Inhibition. Conclusion Both TAM and 5-FU can inhibit cell proliferation, migration and promote apoptosis. TAM can also increase the sensitivity of colon cancer cell line HT-29 to 5-FU.