miR-23b对人肝癌细胞恶性表型及其对仑伐替尼敏感性的影响

Effect of miR-23b on the malignant phenotype and the sensitivity of lenvatinib in human hepatocellular carcinoma cells

目的探讨miR-23b对人肝癌细胞恶性表型及其对仑伐替尼敏感性的影响。方法人肝癌细胞株HepG2、SMMC-7721和QGY-7703细胞分别转染miR-23b mimic及其对照,CCK-8与EdU实验检测细胞增殖能力,Transwell实验检测细胞迁移和侵袭能力的变化情况,管腔形成实验检测细胞的血管生成拟态情况。组间均数比较采用t检验进行分析。结果CCK-8结果显示,转染120 h后miR-23b mimic组的肝癌细胞HepG2和SMMC-7721,其A值分别为0.325±0.011和0.537±0.026,明显低于对照组的0.430±0.017和0.752±0.051(P值均<0.05)。Transwell实验结果显示,miR-23b mimic组肝癌细胞HepG2和SMMC-7721的细胞迁移数为(517.220±32.873)个和(242.327±20.793)个,显著低于对照组的(724.130±15.142)个和(424.432±27.212)个(P值均<0.01);同时miR-23b mimic组的细胞侵袭数为(55.671±7.514)个和(64.670±6.011)个,显著低于对照组的(124.320±11.782)个和(156.204±12.501)个(P值均<0.01)。管腔形成实验显示,miR-23b mimic组肝癌细胞QGY-7703和SMMC-7721的成管分支数为(489.824±42.035)个和(435.201±44.143)个,明显低于对照组的(878.620±31.618)个和(785.430±38.723)个(P值均<0.01)。并且,EdU结果显示miR-23b与仑伐替尼联合用药后,miR-23b mimic组肝癌细胞HepG2和SMMC-7721的EdU染色阳性率为32.905%±1.342%和24.811%±0.820%,显著低于对照组的52.623%±2.441%和38.702%±1.312%(P值均<0.05)。结论miR-23b可抑制人肝癌细胞的增殖、迁移、侵袭和血管拟态形成,并增强人肝癌细胞对仑伐替尼的药物敏感性。

Objective To investigate the effect of miR-23b on the malignant phenotype and the sensitivity of lenvatinib in human hepatocellular carcinoma cells.Methods Human hepatocellular carcinoma cell line HepG2,SMMC-7721 and QGY-7703 were transfected with miR-23b mimic and its control,respectively.CCK-8 and EdU assay were used to detect cell proliferation.Transwell assay were used to detect changes in cell migration and invasion.Tube formation assay were used to detect vasculogenic mimicry formation.The comparison of the mean between groups was analyzed by t-test.Results CCK-8 results showed that the A values of human hepatocellular carcinoma cell line HepG2 and SMMC-7721 in the miR-23b mimic group were 0.325±0.011 and 0.537±0.026,respectively,which were significantly lower than the control group 0.430±0.017 and 0.752±0.051(P<0.05).Transwell assay result showed that the number of cell migration of human hepatocellular carcinoma cell line HepG2 and SMMC-7721 in the miR-23b mimic group was(517.220±32.873)and(242.327±20.793),respectively,which were significantly lower than that of the control group(724.130±15.142)and(424.432±27.212)(P<0.01).Simultaneously,the number of cell invasions in the miR-23b mimic group were(55.671±7.514)and(64.670±6.011),respectively,which were significantly lower than those in the control group(124.320±11.782)and(156.204±12.501)(P<0.01).Tube formation assay showed that the number of tube forming branches of hepatocellular carcinoma cell line QGY-7703 and SMMC-7721 in the miR-23b mimic group was(489.824±42.035)and(435.201±44.143),respectively,which were significantly lower than that of the control group(878.620±31.618)and(785.430±38.723)(P<0.01).In addition,EdU results showed that after miR-23b combined with lenvatinib,the positive rates of EdU staining of hepatocellular carcinoma cell line HepG2 and SMMC-7721 in the miR-23b mimic group were(32.905±1.342)%and(24.811±0.820)%,respectively,which were significantly lower than the control group(52.623±2.441)%and(38.702±1.312)%(P<0.05).Conclusion miR-23b can inhibit the proliferation,migration,invasion and vasculogenic mimicry formation,and enhance the sensitivity of lenvatinib drug in human hepatocellular carcinoma cells.