Keggin型多金属氧簇抑制宫颈癌细胞生长的作用及其机制

Inhibitory effect of Keggin type polyoxometalates on the growth of cervical cancer cells and its mechanism

目的合成Keggin型多金属氧簇mPEG-Si-POM,研究其对宫颈癌细胞(SiHa)的抑制作用及其机制。方法设计合成新型Keggin型多金属氧簇,通过红外线、核磁共振对mPEG-Si-POM结构进行表征,噻唑蓝比色(MTT)法检测其对SiHa细胞半数抑制浓度(IC_(50))的影响。以mPEG-Si-POM处理SiHa细胞设为实验组,未处理细胞设为对照组,采用Hoechst染色检测其对SiHa细胞凋亡的影响,单丹磺酰尸胺(monodansylcadaverin,MDC)染色检测其对细胞自噬的影响,Western blot检测HPV E6、E7蛋白表达的变化。结果红外线、核磁共振结构表征提示mPEG-Si-POM合成成功,Keggin型多金属氧簇mPEG-Si-POM对SiHa细胞具有明显的抑制作用,IC_(50)值为(10.31±0.91)μmol/L。与对照组相比,实验组Hoechst染色细胞凋亡指数为(16.82±3.71)%,差异有统计学意义(P<0.05),MDC显示自噬体比例增加(P<0.05),同时HPV E6、E7蛋白的表达下降(P<0.05)。结论Keggin型多金属氧簇mPEG-Si-POM可通过促进SiHa细胞凋亡和自噬,抑制HPV E6、E7的表达,达到对SiHa细胞生长的抑制作用。

Objective To synthesize Keggin type polyoxometalates,mPEG-Si-POM,and study its inhibitory effect and mechanism on the cervical cancer cells.Methods A new Keggin type polymetallic oxygen cluster was designed and synthesized.The structure of mPEG-Si-POM was characterized by IR and MR.The half inhibitory concentration(IC_(50))of SiHa cells was detected by MTT.SiHa cells were treated with mPEG-Si-POM in experimental group,with untreated cells as control group.The effect of mPEG-Si-POM on the apoptosis of cervical cancer SiHa cells was stained by Hoechst,the autophagy was detected by MDC staining,and the expression of HPV E6 and E7 proteins was detected by Western blot.Results The structural characterization of mPEG-Si-POM by infrared and nuclear magnetic resonance indicated that the mPEG-Si-POM was successfully synthesized.Keggin-type polymetallic oxygen cluster mPEG-Si-POM showed significant inhibitory effect on SiHa cells with IC_(50) value of(10.31±0.91)μmol/L.The apoptosis index of Hoechst staining cells in experimental group was(16.82±3.71)%,and the difference was statistically significant between control group and experimental group(P<0.05).Compared with control group,the proportion of autophagosomes was increased by MDC(P<0.05),and the expression of HPV E6 and E7 protein was decreased(P<0.05).Conclusion Keggin-type polymetallic oxygen cluster mPEG-Si-POM can inhibit the growth of SiHa cells by promoting the apoptosis and the autophagy of SiHa cells and inhibiting the expression of HPV E6 and E7.