SiRNA-Nav1.5 Interferes HSC-3 Cells And Changes In Biological Behavior

Objective In China,cancer is more common in malignant tumors of the oral and maxillofacial regions,and sarcomas are rare.Oral squamous cell carcinoma(OSCC)is the most common in cancer,generally accounting for more than 80%,and its degree of malignancy is high.Regional lymph node metastasis often occurs,and distant metastasis can occur in the late stage.Clinical routine treatment,including radiotherapy,chemotherapy and surgery for tumors.However,the side effects of radiotherapy and chemotherapy are more obvious,and a wide range of surgical resection can cause tissue defects,and due to the metastatic characteristics of OSCC,the recurrence rate is high,the five-year survival rate is only about 50%,so it is urgent to find more effective treatment methods.In recent years,molecular targeted therapy has received more and more attention.Many reports have reported that voltage-gated sodium channels(VGSC)are highly expressed in various cancers and blocking VGSC can effectively reduce the invasion and proliferation of tumors,suggesting that VGSC may be a new target for cancer treatment.In the study of different subtypes of VGSC,it was found that the VGSC subtypes that play a major role in different cancers are different.The previous study of our research group found that the Nav1.5 subtype is closely related to the occurrence and development of OSCC,suggesting that it may become the potential therapeutic targets of OSCC,but no further exploration of its deeper molecular mechanism.In order to explore the role of Nav1.5 in OSCC and its mechanism,this study choose HSC-3(human oral squamous cell carcinoma)cell line to do some experiments in vitro.Methods Two samples of normal oral mucosa tissue as control group,two samples of OSCC as the experimental group were collected from the Department of Oral and Maxillofacial Surgery of The First Affiliated Hospital of Anhui Medical University.Immunohistochemistry was used to detect the expression of Nav1.5 at the tissue level.Immunofluorescence laser confocal microscopy showed the expression of Nav1.5 in HSC-3 cells.CCK8 and Transwell invasion assays were used to test the effect of Nav1.5 on proliferation and invasion of HSC-3 cells after transfected.qRT-PCR and Western blot were used to detect the expression of mRNA and protein of related proteins(PCNA,MMP-2 and MMP-9).All results are presented as the mean ± SD and the data were analyzed by a SPSS 19.0 statistical package.Comparisons between groups were performed using the t-test.Data for multiple comparisons were subjected to one-way ANOVA,each comparison were subjected to SNK q test,and a value of P < 0.05 was considered statistically significant.Results Immunohistochemical results showed that Nav1.5 was positively expressed in oral squamous cell carcinoma,but no significant expression was observed in normal tissues.Confocal results showed positive expression of Nav1.5 in HSC-3 cells.Knockdown of Nav1.5 effectively suppressed the invasion and proliferation of HSC-3 cells.In addition,Nav1.5 silencing inhibited the synthesis of MMP-2,MMP-9 and PCNA.Conclusions Nav1.5 can significantly enhance migration and proliferation of HSC-3 cells.Nav1.5 regulate the biological behavior of oral squamous cell carcinoma may be through regulate the expression of PCNA、MMP-2 and MMP-9.