干扰MACC1协同Wnt信号通路抑制剂对舌鳞癌细胞转移潜能的影响

目的探讨干扰结肠癌转移相关基因1(metastasis-associated in colon cancer 1,MACC1)协同Wnt信号通路抑制剂对舌鳞癌细胞转移潜能的影响。方法以不同浓度的Wnt信号通路抑制剂XAV939处理舌鳞癌细胞,MTT法检测细胞增殖变化。舌鳞癌细胞感染MACC1 shRNA慢病毒,Real-time PCR和Western blot法检测干扰效果。以XAV939处理下调MACC1后的舌鳞癌细胞,MTT法测定细胞增殖变化,划痕愈合实验检测细胞运动能力,MTT法检测细胞黏附能力,Transwell小室实验检测细胞的侵袭和迁移,Western blot法检测细胞中MMP-9及E-cadherin、vimentin蛋白表达水平。结果不同浓度的Wnt信号通路抑制剂XAV939处理后的舌鳞癌细胞增殖能力降低。MACC1 shRNA慢病毒感染后的舌鳞癌细胞中MACC1表达水平降低。下调MACC1和Wnt信号通路抑制剂XAV939处理后的舌鳞癌细胞增殖[100.00% vs (79.81±6.92)%、(50.89±8.30)%]、运动[(76.25±3.47)% vs (51.63±4.20)%、(40.25±3.18)%]、黏附[100.00% vs (77.28±3.50)%、(65.17±5.26)%]、侵袭(80.20±9.33 vs 47.62±6.24、38.25±4.69)、迁移能力(95.36±4.27 vs 63.75±4.51、52.81±3.62)和MMP-9、vimentin蛋白水平均降低,E-cadherin蛋白水平升高,并且两者联合处理后对舌鳞癌细胞增殖[(79.81±6.92)%、(50.89±8.30)% vs (38.69±7.14)%]、运动[(51.63±4.20)%、(40.25±3.18)% vs (31.07±2.24)%]、黏附[(77.28±3.50)%、(65.17±5.26)% vs (52.96±3.21)%]、侵袭(25.14±2.11 vs 47.62±6.24、38.25±4.69)、迁移(35.87±2.05 vs 63.75±4.51、52.81±3.62)能力抑制作用更强。结论干扰MACC1协同Wnt信号通路抑制剂能够下调舌鳞癌细胞增殖、运动、黏附、侵袭、迁移能力。

Interference of MACC1 and Wnt signaling pathway inhibitors in decreasing the metastatic potential of tongue squamous cell carcinoma

Purpose To investigate the effect of interference with MACC1 and Wnt signaling pathway on the metastatic potential of tongue squamous cell carcinoma. Methods Different concentrations of Wnt signaling pathway inhibitor XAV939 were used to treat tongue squamous cell carcinoma. MTT was used to detect cell proliferation. Tongue squamous cell carcinoma was infected with MACC1 shRNA lentivirus. Real-time PCR and Western blot were used to detect the jamming effect. MACC1-down-regulated tongue squamous cell carcinoma was treated with XAV939. Cell proliferation was measured by MTT. Scratch healing test was used to detect cell movement ability. MTT assay was used to detect cell adhesion. Transwell chambers were used to detect invasion and migration. Western blot was used to detect the expression levels of MMP-9 and E-cadherin and vimentin proteins in cells. Results The proliferation of tongue squamous cell carcinoma cells treated with different concentrations of Wnt signaling inhibitor XAV939 decreased. The expression level of MACC1 in tongue squamous cell carcinoma after MACC1 shRNA lentivirus infection decreased. The ability of proliferation [100.00% vs (79.81±6.92)%,(50.89±8.30)%],movement [(76.25±3.47)% vs (51.63±4.20)%,(40.25±3.18)%],adhesion [100.00% vs (77.28±3.50)%,(65.17±5.26)%],invasion (80.20±9.3 vs 47.62±6.24,38.25±4.69),migration (95.36±4.27 vs 63.75±4.51,52.81±3.62) and the levels of MMP-9 and vimentin protein of tongue squamous cell carcinoma cells treated with MACC1 and Wnt signaling pathway inhibitor XAV939 were down-regulated,the level of E-cadherin protein increased. The combined treatment of the two had stronger inhibitory effect on the proliferation [(79.81±6.92)%,(50.89±8.30)% vs (38.69±7.14)%],movement [(51.63±4.20)%,(40.25± 3.18)% vs (31.07±2.24)%],adhesion [(77.28± 3.50)%,(65.17±5.26)% vs (52.96±3.21)%],invasion (25.14±2.11 vs 47.62±6.24,38.25±4.69) and migration (35.87±2.05 vs 63.75±4.51,52.81±3.62) of tongue squamous cell carcinoma cells. Conclusion Interference with MACC1 and Wnt signaling pathway inhibitors can down-regulate the proliferation,movement,adhesion,invasion,migration of tongue squamous cell carcinoma cells.