Experimental Study Of Fluvastatin Sodium On Tongue Squamous Cell Carcinoma

Objective:The aim of this study is to investigate the effect of mevalonate pathway inhibitor fluvastatin sodium(FS)and mevalonate pathway product mevalonate acid(MEV)on the progress of tongue squamous cell carcinoma(TSCC).Analyzing the association among tissue factor(TF),mevalonate pathway(MVP)and TSCC,which will provide a reliable basis for the search of adjuvant therapy drugs that can not only treat oral squamous cell carcinoma(OSCC)but also prevent the thrombotic complications of patients in clinic.Methods:In vitro,different concentrations of FS and FS combined with MEV sequentially treated TSCC cells CAL-27 and HSC-4,respectively.The cell counting kit 8(CCK-8)method was used to analyze the effects of FS and MEV on the proliferation of TSCC cells,flow cytometry was adopted to detect the apoptosis of TSCC cells,wound healing assay was employed to compare the migration ability of cells,and immunofluorescence and western blot were used to detect Ras homolog family member A(RHOA),TF and B-cell lymphoma-2-associated X protein(BAX)expression.In vivo,the intraperitoneal injection was performed at a concentration of 5mg/mL FS(25mg/kg)for 21 consecutive days following successful transplantation of HSC-4 tumors in nude mice.The tumors were measured after the animals were sacrificed,and then the morphological characteristics of the cells were observed by HE staining,and the expression of related proteins was analyzed by immunohistochemical staining.Results:FS could promote the apoptosis of TSCC cells,inhibit cell proliferation in a dose-and time-dependent manner(P<0.05).Both RHOA and TF expressed in TSCC cells.FS decreased RHOA and TF expression with increasing drug concentration(P<0.05).0.1μM,1μM and 10μM MEV could promote the proliferation of TSCC cells.When FS and MEV were combined to treat cells sequentially,MEV significantly promoted the migration of TSCC cells,reversed the inhibition of FS on the proliferation of TSCC cells,and inhibited the pro-apoptotic effect of FS(P<0.05).FS and MEV promoted the expression of BAX and RHOA in cells respectively(P<0.05).FS had no significant effect on the size of HSC-4 transplanted tumors in nude mice and TF expression in the tumors(P>0.05),but decreased the expression of RHOA(P=0.0151)and promoted BAX expression(P=0.0346).Conclusions:FS inhibits the proliferation of TSCC cells CAL-27 and HSC-4,promotes apoptosis,and reduces the expression of RHOA and TF in TSCC cells.MEV can reverse the tumor suppressive effect of FS,promote the proliferation and migration of TSCC cells,inhibit apoptosis,and promote the expression of RHOA in cells.FS has no significant effect on the growth of transplanted tumors and the expression of TF in tumors of the nude mice,but it can reduce RHOA expression in tumor cells and increase BAX expression.Therefore,the mevalonate pathway can regulate the expression of TF and RHOA in TSCC cells and play an important role in the development of TSCC.