ERBB3表达下调对宫颈癌细胞增殖迁移和侵袭的影响

Down-regulation of ERBB3 decreases the proliferation,migration and invasion of cervical cancer cells

目的探讨erb-b2受体酪氨酸激酶3(ERBB3)在调节癌细胞的迁移和侵袭及其在宫颈癌的发生和进展过程中的作用。方法收集2014年4月—2016年12月期间在本院接受治疗的25例宫颈鳞状细胞癌患者和25例宫颈腺癌患者。通过荧光定量PCR(qRT-PCR)检测了宫颈鳞状细胞癌和子宫颈腺癌患者体内肿瘤组织和癌旁组织中ERBB3 mRNA的表达水平。用siRNA转染宫颈鳞状细胞癌细胞沉默ERBB3的表达后,应用Transwell细胞迁移实验检测细胞迁移和侵袭能力,利用CCK-8检测细胞增殖,应用Western blotting检测MTK-1蛋白的表达变化。结果宫颈鳞状细胞癌和宫颈腺癌患者癌组织中ERBB3 mRNA水平均低于其正常组织(P=0.00,P=0.00)。HPV感染对ERBB3蛋白在宫颈鳞状细胞癌细胞系的表达水平为10.30±0.07(HPV阳性)、7.99±0.75(HPV阴性)和正常宫颈细胞系中的的表达水平为3.02±0.47(HPV阳性)、3.16±0.22(HPV阴性),差异均无统计学意义(P均>0.05)。ERBB3 si RNA沉默后宫颈鳞状细胞癌细胞SiHa和C33A的增殖(0.20±0.10,0.16±0.08)、迁移(64.87±0.26,55.02±0.06)和侵袭(49.99±0.06,62.80±0.19)能力显著低于正常宫颈细胞系中SiHa和C33A的增殖(0.86±0.49,0.60±0.34)、迁移(99.99±0.31,100.07±0.23)和侵袭(99.89±0.35,99.89±0.14)能力,差异具有统计学意义(P<0.05)。ERBB3通过si RNA沉默后MTK-1蛋白的表达水平也显着降低。结论 ERBB3的下调很可能通过抑制MTK-1的表达来抑制宫颈癌细胞的增殖、迁移和侵袭,从而抑制肿瘤的发展。

Objective To explore the role if erb-b2 receptor tyrosine kinase 3（ERBB3） in regulating the migration and invasion of cancer cells, and its role in the occurrence and progression of cervical cancer. Methods Totally 25 patients with cervical squamous cell carcinoma and 25 patients with cervical adenocarcinoma were enrolled who were treated in our center from April 2014 to December 2016. Expression level of ERBB3 in patients with cervical squamous cell carcinoma and cervical adenocarcinoma was detected by qRT-PCR. After ERBB3 siRNA silencing on cervical squamous cell, Transwell experiment was used to analyze the capability of migration and invasion, and CCK-8 kits was used to analyze the capability of proliferation, and Western blotting was used to detect S-methyl-5-thioribose kinase 1（MTK-1） protein level. Results qRT-PCR results showed that the expression levels of ERBB3 decreased in cervical squamous cell carcinoma and cervical adenocarcinoma were lower than those in the normal cervical cell lines（P=0.00, P=0.00）. The expression level of HPV infection to ERBB3 protein in cervical squamous cell carcinoma cell lines was 10.30±0.07（HPV positive）, 7.99 ±0.75（HPV negative） and normal cervical cell lines were 3.02±0.47（HPV positive） and 3.16±0.22（HPV negative）, with no statistical significance（P〉0.05）. After ERBB3 si RNA silencing, the capabilities of SiHa and C33 A in cervical squamous cell carcinoma in proliferation（0.20±0.10, 0.16±0.08）, migration（64.87±0.26, 55.02±0.06）, and invasion（49.99±0.06, 62.80±0.19） were significantly lower than those in normal cervical cell lines（P〈0.05）. In addition, the expression level of MTK-1 protein was also significantly reduced after MTK-1 siRNA silencing. Conclusion Down-regulation of ERBB3 can decrease the proliferation, migration and invasion of cervical cancer cells by inhibiting the expression of MTK-1.