VEGF-C Promotes The Proliferation,Invasion And Migration Of Oral Squamous Cell Carcinoma Cells Via Up-regulating The Expression Of Voltage-gated Sodium Channel Subtype Nav1.5

Background & Objective: Oral cancer is a tumor that occurs in the oral and maxillofacial regions of humans.Oral squamous cell carcinoma(OSCC)is the most common,malignant degree,and lymph nodes or distant metastasis often occur in the late stage.Therefore,OSCC is difficult to treat and has a high mortality rate.There is an urgent need to study its specific transfer mechanism to reduce the mortality of OSCC.Voltage-gated sodium channels(VGSC)are transmembrane proteins that control the flow of ions across cell membranes.They are key ion channels for action potentials in excitable tissues and have important physiological functions.Abnormal function of VGSCs will lead to physical dysfunction and trigger multiple physiological diseases.More and more literatures have reported that VGSC have abnormally high expression in a variety of metastatic cancer cells and cancer tissues,such as prostate cancer,breast cancer,cervical cancer,Ovarian cancer,etc.Moreover,it can promote the invasion and metastasis of cancer cells,and blocking the channel activity of VGSC can also significantly reduce the metastasis of tumor cells,and thus speculate that VGSC has a certain relationship with the malignant behavior of cancer cells.In addition,a number of studies have found some molecular mechanisms that regulate the expression and function of VGSC,such as growth factors and hormones.Vascular endothelial growth factor(VEGF-C)induces angiogenesis and promotes lymphangiogenesis and expansion,which is closely related to tumor metastasis.Moreover,VEGF-C expression levels are observed to be elevated in most invasive tumors and are closely related to poor prognosis of cancer patients.This study investigated whether VEGF-C can promote the proliferation,invasion and metastasis of oral squamous cell carcinoma HSC-3 by up-regulating the expression of voltage-gated sodium channel subtype Nav1.5.It further provides new ideas and preliminary theoretical basis for the clinical development of molecular markers and therapeutic targets for oral squamous cell carcinoma metastasis.Methods 1.Western blot was used to detect the effect of VEGF-C on the expression of Nav1.5 protein in oral squamous cell carcinoma HSC-3.2.QRT-PCR was used to detect the effect of VEGF-C on the expression of Nav1.5 m RNA in oral squamous cell carcinoma HSC-3.3.Transwell assay was used to detect the effects of VEGF-C and Nav1.5 on migration and invasion of HSC-3 cells.4.CCK-8 assay was used to detect the effects of VEGF-C and Nav1.5 on the proliferation of HSC-3 cells.Results 1.VEGF-C up-regulated the expression of Nav1.5 m RNA and protein in HSC-3 cells.2.VEGF-C promoted cell proliferation,migration and invasion in a dose-dependent manner.3.VGSC inhibitor TTX effectively blocked the effects of VEGF-C-induced Nav1.5 on proliferation,migration and invasion of HSC-3 cells.Conclusion Vascular endothelial growth factor VEGF-C enhances the proliferation,migration and invasion of oral squamous cell carcinoma HSC-3 by up-regulating the expression of Nav1.5.