藏红花素通过下调STAT3抑制乳腺癌细胞血管内皮生长因子C的表达  

Crocin inhibits the expression of VEGF-C in breast cancer cells by down-regulating STAT3

作　　者：马晓燕[1] 王永霞 邓超[1] 吴寅玮 宿菲[2] 毛春梅[3] 张雅芳[1] 刘宝全[1] Ma Xiaoyan;Wang Yongxia;Deng Chao;Wu Yinwei;Su Fei;Mao Chunmei;Zhang Yafang;Liu Baoquan(Department of Anatomy,the Fourth Affiliated Hospital,Harbin Medical University,Harbin 150001,China;Science and Technology College of Bioinformatics,the Fourth Affiliated Hospital,Harbin Medical University,Harbin 150001,China;Department of Pediatrics,the Fourth Affiliated Hospital,Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学人体解剖学教研室,哈尔滨150001 [2]哈尔滨医科大学生物信息学教研室,哈尔滨150001 [3]哈尔滨医科大学附属第四医院儿科,哈尔滨150001

出　　处：《解剖学杂志》2024年第6期493-499,共7页Chinese Journal of Anatomy

基　　金：国家自然科学基金青年项目(61801151);黑龙江省自然科学基金(LH2023H013,LH2021F053)。

摘　　要：目的:探讨藏红花素(Crocin)对乳腺癌细胞增殖、迁移及血管内皮生长因子C(VEGF-C)表达的影响及其机制。方法:使用Crocin处理乳腺癌MDA-MB-231细胞和ZR-75-30细胞,采用MTT法检测细胞增殖,细胞划痕实验检测细胞迁移;应用信号转导和转录激活子3(STAT3)激动剂Colivelin干预Crocin处理2种乳腺癌细胞,分为对照组、Crocin组和Crocin+Colivelin组,RT-qPCR和免疫印迹检测VEGF-C mRNA和蛋白表达,免疫印迹检测STAT3和磷酸化STAT3(p-STAT3)表达。结果:Crocin能够抑制MDA-MB-231细胞和ZR-75-30细胞的增殖,且与药物浓度及时间呈正相关。2种乳腺癌细胞48 h的IC50值分别为2376μmol/L和2654μmol/L。Crocin处理后,与对照组相比,2种乳腺癌细胞的迁移能力明显降低,VEGF-C的mRNA和蛋白表达水平明显降低,同时p-STAT3的表达水平显著降低;Crocin+Colivelin组的p-STAT3和VEGF-C表达水平恢复至接近对照组水平,且明显高于Crocin组。结论:Crocin能够抑制乳腺癌细胞的增殖和迁移,其机制涉及通过下调STAT3抑制乳腺癌细胞VEGF-C的表达。Objective:To explore the effects and mechanisms of Crocin on breast cancer cell proliferation,migration,and vascular endothelial growth factor C(VEGF-C)expression.Methods:MDA-MB-231 and ZR-75-30 breast cancer cells were treated with different concentrations of Crocin.MTT and cell scratch were used to detect cell proliferation and migration.The STAT3 agonist Colivelin was used to intervene in the Crocin-treated breast cancer cells.RT-qPCR and Western blotting were used to detect changes in the expression of VEGF-C and STAT-3.Results:Crocin could inhibit the proliferation of MDA-MB-231 and ZR-75-30 cells,and was positively correlated with drug concentration and time.The IC50 values of MDA-MB-231 and ZR-75-30 cells at 48 hours were 2376μmol/L and 2654μmol/L,respectively.After Crocin treatment for 24 h and 48 h,the migration ability of both cells was significantly reduced.Besides,the mRNA and protein expression levels of VEGF-C in two breast cancer cells were significantly reduced,and the expression level of p-STAT3 was also significantly reduced.The expression levels of p-STAT3 and VEGF-C in the Crocin+Colivelin group were restored to levels close to that of the control group,and were significantly higher than those in the Crocin group.Conclusion:Crocin can inhibit the proliferation and migration of breast cancer cells,and it inhibits the expression of VEGF-C in breast cancer cells by down-regulating STAT3.

关 键 词：藏红花素 乳腺癌 血管内皮生长因子C 信号转导和转录激活子3 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]