Effect Of Metformin Combined With Shikonin On Biological Behavior Of Human Nasopharyngeal Carcinoma Cell CNE-2Z

Background:Nasopharyngeal carcinoma(NPC)is a malignant tumor of the head and neck that can occur in any age group.Its location is insidious and its symptoms are mild,and it is often detected only after extensive invasion or lymphatic metastasis,and most patients are already at an advanced stage when they are diagnosed,with a very poor prognosis.Metformin is a first-line hypoglycemic agent,and in recent years,some studies have shown that it can also inhibit tumor growth,and metformin has been found to show excellent therapeutic potential in hepatocellular carcinoma,thyroid cancer,lung cancer,and gastric cancer.Shikonin is a naphthoquinone derived from Comfrey,which can inhibit tumor cells by reducing PKM2 synthesis and thus inhibiting glycolysis,as well as promoting necrotic apoptosis.The aim of this study is to investigate the effect of metformin and shikonin combination on CNE-2Z cells and its mediating pathway,and to provide a better solution for the clinical treatment of nasopharyngeal carcinoma.Methods: The experiment was divided into four groups: blank group,metformin group,shikonin group and metformin + shikonin group.The proliferation of CNE-2Z cells was detected by MTT assay,and the apoptosis of CNE-2Z cells by Annexin V FITC/PI double staining.The ability of invasion and migration was detected using invasion and migration assay,and the colony-forming ability was detected by colony formation test.The expressions of Bcl-2,Bax,MMP9,RIP1 and RIP3 in CNE-2Z cells were detected using Western blot.Result: MTT results showed that both drugs had inhibitory effects on cell proliferation and the inhibition rate of the combined group was significantly lower than that of the single drug group and was time-dependent(P<0.05);2.Western blot showed that the Bcl-2/Bax ratio and MMP9 expression in the metformin+purpurea group were significantly lower than those in the other three groups;the expression of RIP1 and RIP3 were significantly higher than those in the other three groups(P<0.05).Conclusion: Metformin and shikonin may inhibit CNE-2Z cell proliferation,promote apoptosis,and alter the expression of related proteins RIP1,RIP3,Bcl-2,Bax and MMP9 to inhibit tumor growth and invasion,thus achieving anti-tumor effects.