Slit2对甲状腺乳头状癌生物特性的影响

Effect of Slit2 on the Biological Characteristics of Papillary Thyroid Carcinoma

目的探讨Slit2对甲状腺乳头状癌(PTC)生物特性的影响及其机制。方法选取经CT和病理确诊的PTC患者50例,术中取甲状腺癌组织及相应的癌旁正常组织,实时荧光定量PCR(RT-qPCR)检测Slit2 mRNA的表达。将Slit2/pCMV6-Entry重组质粒或pCMV6-Entry对照质粒转染至人甲状腺乳头状癌BHT101细胞中,检测细胞增殖、迁移和侵袭,免疫共沉淀技术检测β-连环蛋白/E-钙黏蛋白相互结合情况,RT-qPCR和Western Blot检测Rac1的表达和活性。结果Slit2 mRNA在甲状腺癌组织中的表达显著低于其在癌旁组织中的表达(P<0.05)。Slit2 mRNA在转移癌患者的甲状腺癌组织中的表达显著低于其在无转移癌患者中的表达(P<0.05)。Slit2显著抑制甲状腺癌细胞的增殖、迁移和侵袭(P<0.05),增加E-钙黏蛋白和β-连环蛋白的相互结合(P<0.05),降低Rac1活性、p-Rac1、Rac1 mRNA和蛋白的表达(P<0.05)。结论Slit2抑制甲状腺癌的发生发展,并通过增加膜β-连环蛋白/E-钙黏蛋白的结合抑制甲状腺癌细胞增殖,通过抑制Rho GTP酶Rac1抑制甲状腺癌细胞迁移和侵袭。

Objective To investigate the effect and its mechanism of Slit2 on the biological characteristics of papillary thyroid carcinoma(PTC).Methods 50 patients with PTC diagnosed by CT and pathology were selected.Thyroid cancer tissues and corresponding adjacent normal tissues were collected during operation.Real-time quantitative PCR(RT-qPCR)was used to detect the expression of Slit2 mRNA.Slit2/pCMV6-Entry recombinant plasmids or pCMV6-Entry control plasmids were transfected into human thyroid papillary carcinoma BHT101 cells.Cell proliferation,migration and invasion were detected.Co-immunoprecipitation was used to detect the binding of β-catenin with E-cadherin.The expression and activity of Rac1 were detected by RT-qPCR and Western Blot.Results The expression of Slit2 mRNA in thyroid carcinoma tissues was significantly lower than that of adjacent tissues(P<0.05).The expression of Slit2 mRNA in thyroid cancer tissues of patients with metastatic cancer was significantly lower than that in patients without metastasis(P<0.05).Slit2 significantly inhibits the proliferation,migration and invasion of thyroid cancer cells(P<0.05),increases the binding of E-cadherin and β-catenin(P<0.05),decreases activity of Rac1 and expressions of p-Rac1,Rac1 mRNA and protein(P<0.05).Conclusion Slit2 inhibits the progression and development of thyroid cancer,and it inhibits the proliferation of thyroid cancer cells by increasing the binding of membraneβ-catenin/E-cadherin,and inhibits the migration and invasion of thyroid cancer cells by inhibiting expression of Rho GTPase Rac1.