1.Study on effect and mechanism of HIF -1 α silencing combined with methylselenenic acid on proliferation and apoptosis of cervical cancer cells
Zhenhao Li ; Yaofeng Hou ; Ling Li ; Xuanyu Huang ; Wanyu Liu ; Aixia Zhang ; Nan Wang
Acta Universitatis Medicinalis Anhui 2022;57(12):1954-1959
Objective :
To investigate the influence and molecular mechanism of hypoxia-inducing factor-1 α( HIF- 1 α) gene silencing combined with methyl selenenic acid (MSA) on cervical cancer cell proliferation,apoptosis and cell migration.
Methods :
HeLa cells were transfected with HIF-1 interference RNA and negative control RNA.Af- ter transfection for 48 h,cells were stimulated with MSA for 24 h,and cell proliferation was determined by CCK-8 assay and colony formation.Apoptosis was determined by flow cytometry combined with Annexin V-FITC / PI.The expression levels of HIF-1α , Bcl-2 ,and E-cadherin were detected by Western blot assay. Cell migration ability was determined by Transwell assay. RNA-seq analysis was used to investigate the differentially expressed genes and differential signaling pathways.
Results :
Compared with the control group,interfering with HIF-1α combined with MSA significantly inhibited cell proliferation (P <0.01) .Flow cytometry results showed that the combined drug group significantly induced apoptosis.Transwell results showed that interfering with HIF-1α combined with MSA
inhibited HeLa cell migration.Compared with the control group,interfering with HIF-1α combined with MSA down- regulated the expression of Bcl-2 and up-regulated the expression of E-cadherin. RNA-sequencing combined with signal pathway enrichment results showed that the expression of apoptotic signal pathway and downstream genes was inhibited.
Conclusion
HIF-1α gene silencing combined with MSA can synergically inhibit the proliferation and induce apoptosis of cervical cancer cells,and its regulatory mechanism may be related to the expression of Bcl-2 family proteins and the inhibition of p53 signaling pathway.