二羟基呫吨酮促进肝癌细胞焦亡抑制增殖转移

Dihydroxyxanthone promote cell pyroptosis and inhibit the proliferation and metastasis of hepatocellular carcinoma cells

目的探讨二羟基呫吨酮对于肝癌细胞焦亡、增殖及转移的影响及机制。方法将人肝癌细胞分为4组:空白组细胞不使用药物干预,低剂量组细胞采用5μmol/L浓度二羟基呫吨酮干预,中剂量组细胞采用10μmol/L浓度二羟基呫吨酮干预,高剂量组细胞采用20μmol/L浓度二羟基呫吨酮干预。然后检测细胞存活率、焦亡、转移情况,以及细胞焦亡相关蛋白表达。结果经二羟基呫吨酮干预后,肝癌细胞存活率显著降低[空白组100%,低剂量组(75.36±10.25)%,中剂量组(52.64±10.24)%,高剂量组(35.56±7.14)%]而焦亡率[空白组(3.10±1.02)%,低剂量组(9.86±3.56)%,中剂量组(15.56±2.22)%,高剂量组(21.58±3.55)%]和侵袭抑制率显著升高[空白组0%,低剂量组(26.85±8.63)%,中剂量组(48.96±10.57)%,高剂量组(69.85±10.14)%];半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-1、白细胞介素(IL)-18、IL-1β表达量显著升高。并且这些影响与二羟基呫吨酮存在剂量依赖关系。结论二羟基呫吨酮抑制肝癌细胞增殖、转移、存活的机制与诱导其焦亡相关。

Objective To investigate the effects and mechanisms of dihydroxyxanthone on the pyroptosis,proliferation and metastasis of hepatocellular carcinoma cells.Methods Human hepatocellular carcinoma cells were divided into four groups.No drug intervention cell was used in blank group,5μmol/L dihydroxycarbazone was used in low dose group,10μmol/L dihydroxycarbazone was used in medium dose group,and 20μmol/L dihydroxycarbazone was used in high dose group.Then the cell survival rate,pyroptosis and metastasis,as well as pyroptosis protein expression were detected.Results After intervention with dihydroxyxanthone,the survival rate of hepatocellular carcinoma cells decreased significantly(100%in blank group,75.36%in low dose group,52.64%in middle dose group,35.56%in high dose group,7.14)and the pyroptosis rate(3.10%in blank group,9.86%in low dose group,15.56%in middle dose group,21.58%in high dose group,and 3.55)increased significantly.Invasion inhibition rate was significantly increased[0%in blank group,(26.85±8.63)%in low-dose group,(48.96±10.57)%in middle-dose group and(69.85±10.14)%in high-dose group],and the expression levels of cysteinyl aspartate-specific protease(Caspase)-1,interleukin(IL)-18 and IL-1βwere significantly increased.These effects are dose-dependent with dihydroxyxanthone.Conclusion Dihydroxyxanthone inhibits the proliferation,metastasis and survival of hepatocellular carcinoma cells,and the mechanism is related to the induction of pyroptosis.