FOX03a通过下调VEGF—A抑制乳腺癌增殖和侵袭转移  

FOXO3a inhibits proliferation and invasion of breast cancer by down regulating VEGF-A

作　　者：宋莹[1] 邱惠思 刘浩[1] 贺智敏[1] 

机构地区：[1]广州医科大学附属肿瘤医院肿瘤研究所,广州恶性肿瘤治疗转化医学重点实验室,广州510095

出　　处：《中国医师杂志》2017年第2期168-172,共5页Journal of Chinese Physician

基　　金：国家自然基金资助项目（81402497）,广东省医学科研基金（A2016413）

摘　　要：目的探讨叉头转录因子O3a（FOXO3a）通过下调血管内皮生长因子（VEGF）-A抑制乳腺癌细胞增殖和转移的作用。方法使用SiRNA干扰乳腺癌MCF-7和MDA—MB-231细胞中FOXO3a的表达，采用细胞增殖曲线和细胞克隆法检测干扰后细胞增殖改变；采用细胞划痕实验和transwell实验检测干扰后细胞迁移能力的改变，通过realtime RT—PCR和Western blot技术检测干扰后细胞中VEGF-A的mRNA和蛋白表达的改变，检测20例乳腺癌患者的乳腺癌组织及其配对癌旁正常乳腺组织中FOX03a和VEGF—AmRNA表达情况。结果干扰FOXO3a后MCF-7和MDA—MB-231细胞的增殖能力及侵袭转移能力增强（P〈0．05），且VEGF—A的mRNA和蛋白表达均上调；20例乳腺癌组织中有15例（75％）FOXO3a表达低于对应癌旁组织，VEGF—A表达高于对应癌旁组织，FOXO3a和VEGF—A表达呈高度负相关（r=-0．458，P〈0．01）。结论FOXO3a对乳腺癌细胞增殖和侵袭转移具有抑制作用，该作用可能与其抑制VEGF—A表达有关。Objective To explore the role of forkhead box protein O3a （FOXO3a） in inhibiting the proliferation and metastasis of breast cancer cells by downregulation of vascular endothelial growth factorA （VEGF-A）. Methods Cell proliferation bioassay and plate clone formation assay were used to compare the changes of proliferation after siRNA interference. Wound healing and Transwell were used to compare the changes of invasion metastasis after interference. Meanwhile, the changes of VEGF-A expression in the cells before and after interference were compared by real time polymerase chain reaction （RT-PCR） and Western blot. Furthermore, the expressions of mRNA FOXO3a and VEGF-A were detected in 20 cases of breast cancer patients in breast cancer tissues and adjacent normal breast tissues. Results The MCF-7 and MDA-MB-231 cells were increased in cell proliferation and invasion after interference. Further studies found that mRNA and protein expression of VEGF-A were up-regulated in MCF-7 and MDA-MB-231 cells after interference. In vivo the expression of FOXO3a was lower in 15 cases of cancer compared to normal tissues, and the expression of VEGF-A was high in 15 cases of cancer （75%）. FOXO3a and VEGF-A expression was highly negatively correlated. Conclusions This study showed that FOXO3a could inhibit the proliferation and invasion of breast cancer ceils, which might be regulated by VEGF-A. It provides an important theoretical evidence for targeted inhibition of breast cancer metastasis.

关 键 词：叉头转录因子类 血管内皮生长因子A 乳腺肿瘤 肿瘤侵润 肿瘤转移 细胞增殖 

分 类 号：R737.9[医药卫生—肿瘤]