Study On The Mechanism Of IL18 On Tongue Cancer Cell Line CRL1623

Objectives: Lymph node metastasis in tongue squamous cell carcinoma(TSCC)and anatomical features such as rich lymphatics and blood circulation in the tongue,so tongue cancer is prone to infiltration and metastasis.Although current surgical techniques and adjunctive treatment methods continue to improve,the 5-year survival rate of tongue cancer has not improved significantly.Postoperative recurrence of tongue cancer and regional lymph node metastasis are often the major causes of treatment failure.Some studies have suggested that IL18 is an anti-tumor agent with good application prospects.At the same time,we will further evaluate the promoting role of IL-18.In order to combine the use of a certain drug,to block its cancer-promoting pathways and to synergize its anti-cancer effect,to promote its role in cancer treatment and provide a theoretical basis for its clinical application.Methods: Firstly,p CDNA3.1/IL18 eukaryotic expression vector was constructed and IL-18 was over-expressed in CRL1623 to detect the migration and invasion ability of tongue cancer cells and detect the expression changes of p38,P-p38 and ?-catenin..We found that over-expressed IL-18 promotes the invasion and metastasis of tongue cancer cells,while over-expressed IL-18 inhibits the activity of p38 but activates ?-catenin activity.To explore the effect of IL-18 on the migration and invasion of oral squamous cell carcinoma,we also examined the expression of metastasis-associated factors in xenograft tumors in nude mice,and preliminary confirmed the mechanism of IL-18 in promoting the metastasis of tongue cancer cells.Results: 1 Eukaryotic expression vector of mammalian cell of Interleukin-18 gene was constructed,and the eukaryotic vector p CDNA3.1 and IL-18 fragments were successfully connected;2 Transwell results showed that tongue squamous cell carcinoma overexpressing IL-18,The migration and invasion ability of the cells were significantly higher than those of the control group(P<0.01);3 IL-18-mediated activation of p38 and P-p38 in TSCC cells.To further explore the possible mechanism of IL-18 overexpression on the activity of TSCC cells,we examined the expression of p38,p-p38 and ?-catenin proteins in CRL1623-IL18 and CRL1623-Vec.The results showed that there was no change in p38 in the two groups,but the expression of p-p38 in CRL1623-IL18 was down-regulated and ?-catenin was up-regulated;4 IL-18 overexpressing in nude mice transplanted with empty plasmids The expression of IL-18(P<0.01),?-catenin(p=0.028)and TNKS2 protein increased(p=0.045),the expression of E-cadherin decreased(p=0.045),and the expression of N-cadherin in the transplanted tumor tissue.Increased(p=0.068),E-cadherin/N-cadherin ratio was significantly lower(p=0.031).Conclusions: We speculate that the overexpression of IL-18 in tongue cancer has a dual role,that is,activation of GSK-3? by inhibiting the p38 MAPK pathway plays a tumor suppressive role;and TNKS2 activates the Wnt/?-catenin pathway to promote tongue cancer cells.EMT occurs,promotes cell metastasis,and plays a cancer-promoting role.