Cryptotanshinane Sensitizes Antitumor Effect Of Paclitaxel On Tongue Squamous Cell Carcinoma Growth By Inhibiting The JAK/STAT3 Signaling Pathway

Objective In the present study,we further confirmed that STAT3 inhibition is required for the combination treatment with paclitaxel in TSCC cells,suggesting Cryptotanshinone might be a promising candidate for TSCC clinical treatment.Method We examined STAT3 expression levels in neoplastic tissues of TSCC and evaluated the correlation between STAT3 expression and the prognosis of TSCC patients.This study was performed in two tongue squamous cancer cell lines(CAL 27 and SCC 9).The 50% effective dose of Cryptotanshinone and paclitaxel alone was detected by CCK-8 assay and the cell proliferation ability was evaluated using clonogenic assay.Flow cytometry was used to detect cell apoptosis and cycle.The migration and invasion ability were assessed by transwell and scratch assay.The expression levels of p-STAT3(Ser727),p-STAT3(Try705),apoptosis-or cycle-related protein in both cell lines after Cryptotanshinone or combination treatment group were determined by western blot assay.Result The rate of STAT3 expression was 44 %(22/50)in primary foci tissues and 10 %(5/50)in para-cancer tissues,respectively.Furthermore,the expression level of STAT3 is associated with tumor clinical stage,pathologic stage and lymph node metastasis.As a result,western blot assay displayed a high expression of STAT3 in parental cell lines CAL 27 and SCC 9.CCK-8,flow cytometry,transwell migration and scratch assay indicated that Cryptotanshinone attenuated proliferation,invasion and migration capacities and enhanced chemosensitivity to paclitaxel in TSCC cell lines in vitro by inhibiting the phosphorylation of STAT3 Try 705 and Ser 727.Western blot assay showed that down-regulated CDK2,Bcl-2 and Matrix Metalloproteninases(MMPs)protein accompanied by up-regulated Bax,E-cadherin and ?-catenin in combination treatment group.Conclusion In conclusion,our findings provide insights that Cryptotanshinone reduces the cell proliferation,invasion and migration ability and sensitizes antitumor effect of paclitaxel on TSCC growth by suppresses phosphorylation of STAT3 Try 705,which might be exploited as a novel therapeutic strategy to suppress paclitaxel resistance.