索拉非尼与阿帕替尼对人肝癌SMMC-7721细胞的抑制作用比较

Comparison of sorafenib versus apatinib inhibitory effects on SMMC-7721 cells

目的比较索拉非尼及阿帕替尼对人肝癌SMMC-7721细胞的抑制作用。方法设置药物浓度6.25μg/ml、12.5μg/ml、50μg/ml、100μg/ml、200μg/ml的索拉非尼(索拉非尼组)与阿帕替尼(阿帕替尼组)分别作用于SMMC-7721细胞。采用四甲基偶氮唑盐[3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide,MTT]比色法检测索拉非尼、阿帕替尼对SMMC-7721细胞增殖的抑制作用,细胞划痕实验比较两种药物对SMMC-7721细胞迁移的影响,酶联免疫吸附测定法(enzymelinked immunosorbent assay,ELISA)检测两种药物作用细胞后,其上清液中血管内皮生长因子(vascular endothelial growthfactor,VEGF)、肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、白介素6(interleukin-6,IL-6)的浓度。结果 (1)随着给药浓度的增加,索拉非尼、阿帕替尼对细胞增殖的抑制作用增强;且同一药物浓度下,索拉非尼组生长抑制率均高于阿帕替尼组,差异有统计学意义(P<0.001)。(2)索拉非尼组、阿帕替尼组和对照组细胞迁徙面积比率分别为(0.26±0.012)%、(0.46±0.011)%和(0.66±0.023)%,三组迁徙面积比率差异有统计学意义(F=746.020,P<0.001),进一步两两比较显示,索拉非尼组的迁徙面积小于阿帕替尼组,差异有统计学意义(P<0.05)。(3)药物作用后细胞上清液中VEGF、TNF-α、IL-6浓度,索拉非尼组均低于阿帕替尼组,差异均有统计学意义(P<0.05)。结论索拉非尼、阿帕替尼都对SMMC-7721细胞的增殖、迁移、细胞因子均有抑制作用,且索拉非尼作用强于阿帕替尼。

Objective The study objective was to compare the inhibitory effects of sorafenib and apatinib on SMMC-7721 cells. Methods Concentrations of 6.25, 12.5, 50, 100 and 200 μg/ml sorafenib（sorafenib group） and apatinib（apatinib group） were respectively placed in SMMC-7721 cells. The inhibition effects of sorafenib and apatinib on SMMC-7721 cells were measured by [3-（4, 5）-dimethylthiahiazo（-z-y1）-3, 5-di-phenytetrazoliumromide,MTT] assay. A cell scarification test was applied to compare the migration effects of the two drugs on SMMC-7721 cells. Levels of vascular endothelial growth factor（VEGF）, tumor necrosis factor alpha（TNF-α） and interleukin-6（IL-6） in the supernatant of the two groups were detected by enzyme-linked immunosorbent assay（ELISA）. Results（1） With the increase of drug concentration, the ability to suppress cell proliferation of sorafenib and apatinib were both enhanced. The inhibition rate of cell growth in sorafenib group was higher than that of the apatinib group in each drug concentration, and the differences were statistically significant（P〈0.001）.（2） Migration area ratios of the sorafenib group, apatinib group and control group were（0.26±0.012）%,（0.46±0.011）% and（0.66±0.023）% respectively. There was significant difference in the ratio of the migration area among the three groups（F=746.020, P〈0.001）. Further comparison showed that the migration area in sorafenib group was significantly lower than that in apatinib group, and the difference was statistically significant（P〈0.001）.（3） The levels of VEGF, TNF-αand IL-6 of the sorafenib group were lower than those of apatinib group in cell supernatant after drug action, and the difference was statistically significant（P〈0.05）. Conclusions Both sorafenib and apatinib can inhibit proliferation and migration of SMMC-7721 cells and reduce cell factors, and the action of sorafenib is stronger than that of apatinib.