Mfn2调控VEGFR2/PI3K促进卵巢癌种植转移的机制研究

Study on the mechanism of Mfn2 regulating VEGFR2/PI3K to promote ovarian cancer implantation and metastasis

目的 探讨线粒体融合蛋白2(Mfn2)对卵巢癌种植转移的作用以及其可能的分子机制。方法 选取2019年6月至2021年6月于南京医科大学附属苏州医院就诊治疗的86例卵巢癌患者作为研究对象,对比癌组织和癌旁组织Mfn2、血管内皮生长因子受体2(VEGFR2)、磷酸酰肌醇3激酶(PI3K)蛋白表达,分析Mfn2、VEGFR2、PI3K蛋白表达与相关病理特征的关系。构建Mfn2上调/下调卵巢癌SKOV-3细胞株并验证Mfn2、VEGFR2、PI3K的表达。结果 Mfn2、VEGFR2、PI3K在肿瘤组织中的阳性表达率高于癌旁组织,差异均有统计学意义(χ^(2)=4.597、6.456、3.930,P=0.032、0.011、0.047);不同FIGO分期、淋巴结转移、远处转移情况及生存情况中,卵巢组织中Mfn2、VEGFR2、PI3K蛋白表达比较,差异均有统计学意义(P<0.05)。与NC组对比,Mfn2上调组卵巢癌SKOV-3细胞中Mfn2 mRNA相对表达量和Mfn2、VEGFR2、PI3K蛋白、显著上调(P<0.05);与shNC组对比,shMfn2下调组卵巢癌SKOV-3细胞中Mfn2mRNA相对表达量和Mfn2、VEGFR2、PI3K蛋白显著下调(P<0.05)。结论 下调Mfn2表达与VEGFR2、PI3K表达水平可以预防卵巢癌种植转移。

Objective To investigate the role of the mitochondrial fusion protein 2(Mfn2)in ovarian cancer implantation and metastasis and to explore its potential molecular mechanism.Methods The study selected 86 patients with ovarian cancer who were treated at Suzhou Hospital Affiliated with Nanjing Medical University from June 2019 to June 2021 as the study subjects.The protein expressions of Mfn2,vascu-lar endothelial growth factor receptor 2(VEGFR2)and phosphoinositide 3-kinase(PI3K)in cancer tissue and adjacent tissue were compared to analyze the relationship between Mfn2,VEGFR2 and PI3K protein expres-sion and related pathological features.An up-regulated/down-regulated SKOV-3 cell line was constructed to verify the expression of Mfn2,VEGFR2 and PI3K.Results The positive expression rates of Mfn2,VEGFR2 and PI3K in tumor tissues were higher than those in para-cancer tissues(χ^(2) values were 4.597,6.456 and 3.930,with P values of 0.032,0.011 and 0.047,respectively).There were statistically significant differences in the expression of Mfn2,VEGFR2 and PI3K in ovarian tissues at different FIGO stages,lymph node metas-tasis,distant metastasis and survival conditions(P<0.05).Compared with the NC group,the relative expres-sion of Mfn2 mRNA and Mfn2,VEGFR2 and PI3K proteins in SKOV-3 cells of ovarian cancer in the Mfn2 up-regulated group were significantly up-regulated(P<0.05).Compared with the shNC group,the relative expres-sion of Mfn2 mRNA and Mfn2,VEGFR2,and PI3K proteins in SKOV-3 cells of ovarian cancer in the down-regulated shMfn2 group were significantly down-regulated(P<0.05).Conclusion Down-regulating Mfn2 ex-pression and VEGFR2 and PI3K expression levels can prevent ovarian cancer implantation and metastasis.