The STAT-3 inhibitor WP1066 promotes oral squamous cell carcinoma invasiveness by cisplatin in vitro / 天津医药

ABSTRACT

Objective To investigate the effect of signal transducers and activators of transcription 3(STAT-3)on sen-sitizing oral squamous cell carcinoma to cis-dichlorodiamineplatinum via downregulating miRNA-21. Methods Tscca and Tca8113P160 human tongue squamous cell carcinoma cell lines were employed in this study. WP1066 was used to suppress STAT-3 signaling pathway. Cells were divided into three groupsdimethyl sulphoxide (DMSO) group, cis-dichlorodiamine-platinum (DDP) group and WP1066+DDP group. Transcription level of miR-21 was assessed by real-time PCR, while the expression levels of STAT-3, p-STAT-3, tissue inhibitor of metalloproteinase-3 (TIMP-3) and matrix metalloproteinase-2/9 (MMP-2/9 ) were evaluated by Western blot assay. Matrigel matrix and transwell assay were used to determine cancer cell colony formation and invasive ability respectively. Expression level of miR-21 was examined by luciferase reporter gene as-say. Results Expression levels of STAT-3, pSTAT-3 and miR-21 were significantly suppressed by WP1066 treatment. The diameters of culture colony in cells treated with WP1066 and DDP were smaller than those in control group. The number of tongue cancer cells that migrated through the transwell membrane in WP1066 and DDP treated group was less than that in control group. Additionally, MMP-2/9 expression decreased while TIMP-3 increased dramatically in both cell lines in WP1066+DPP group compared to the other two groups. Conclusion Reduction of STAT-3 can sensitize oral squamous cell carcinoma to cis-dichlorodiamineplatinum via downregulating miR-21. Our study shows that DDP, in combination with WP1066, might be used as a potential target in the treatment of human oral squamous cell cancer.