基于JAK2/STAT3信号通路探讨阳和汤含药血清对肿瘤相关脂肪微环境中乳腺癌细胞迁移、侵袭的影响  

Discussion on the Effects of Yanghe Decoction Containing Serum on Migration and Invasion of Breast Cancer Cells in Tumor Related Fat Microenvironment Based on the JAK2/STAT3 Signaling Pathway

作　　者：骆金磊 江成杰 窦建卫[2] LUO Jinlei;JIANG Chengjie;DOU Jianwei(School of Basic Medicine,Gansu University of Chinese Medicine,Gansu Provincial Engineering Laboratory for the Development of New Chinese Medicine Products,Key Laboratory of Traditional Chinese Medicine Formula Innovation and Transformation in Gansu Province,Lanzhou 730000,China;School of Medicine,Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]甘肃中医药大学基础医学院,甘肃省中药新产品创制工程实验室,甘肃省中医方药挖掘与创新转化重点实验室,甘肃兰州730000 [2]西安交通大学医学部,陕西西安710061

出　　处：《中国中医药信息杂志》2025年第3期105-111,共7页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(82074374);陕西省创新能力支撑计划(2023-CX-PT-19)。

摘　　要：目的基于JAK2/STAT3信号通路探究阳和汤含药血清对肿瘤相关脂肪细胞条件培养基(CAAcm)干预后的乳腺癌BT-549细胞迁移、侵袭的影响及作用机制。方法选取小鼠胚胎成纤维细胞系3T3-L1,以成脂诱导分化培养基诱导液诱导获得成熟脂肪细胞。采用SD大鼠制备阳和汤含药血清,将BT-549细胞与成熟脂肪细胞共培养获取CAAcm,Transwell实验分别检测CAAcm干预前后BT-549细胞迁移和侵袭能力。将CAAcm干预后的BT-549细胞分为空白血清组、阳性药组及阳和汤低、中、高剂量组,分别予10%相应血清培养,CCK-8法检测BT-549细胞增殖情况,划痕实验检测细胞横向迁移情况,Transwell实验检测细胞纵向迁移和侵袭能力,Western blot检测细胞Janus激酶2(JAK2)、信号转导与转录激活子3(STST3)、血管内皮生长因子(VEGF)、缺氧诱导因子-1α(HIF-1α)蛋白表达。结果CAAcm干预对BT-549细胞迁移、侵袭有促进作用。与空白血清组比较,阳和汤低、中、高剂量组BT-549细胞生长抑制率显著升高(P<0.05,P<0.01),划痕愈合率显著降低(P<0.05,P<0.01),迁移细胞数、侵袭细胞数显著减少(P<0.01),JAK2、STAT3、VEGF、HIF-1α蛋白表达显著降低(P<0.05,P<0.01)。结论阳和汤含药血清可抑制CAAcm干预后的BT-549细胞增殖、迁移、侵袭,其机制可能与抑制JAK2、STAT3、VEGF、HIF-1α蛋白表达有关。Objective To investigate the effects and mechanism of Yanghe Decoction containing serum on the migration and invasion of BT-549 cells intervened by conditioned medium of cancer-associated adipocytes(CAAcm)based on the JAK2/STAT3 signaling pathway.Methods 3T3-L1 mouse embryonic fibroblasts were induced to differentiate into mature adipocytes using adipogenic induction medium.Yanghe Decoction containing serum was prepared from SD rats.BT-549 cells were co-cultured with mature adipocytes to obtain CAAcm.Transwell assay was used to detect the migration and invasion ability of BT-549 cells before and after intervention with CAAcm.BT-549 cells after CAAcm intervention were divided into blank serum group,positive drug group and Yanghe Decoction low-,medium-and high-dosage groups,and cultured with 10%corresponding serum.Cell proliferation was assessed using the CCK-8 assay,scratch assay was performed to evaluate the lateral migration of BT-549 cells,Transwell assay was conducted to evaluate the vertical migration and invasion ability of BT-549 cells,Western blot was performed to detect the expressions of proteins including JAK2,STAT3,VEGF and HIF-1α.Results CAAcm intervention had a promoting effect on the migration and invasion of BT-549 cells.Compared with the blank serum group,the growth inhibition rate of BT-549 cells significantly increased in Yanghe Decoction low-,medium-and high dosage groups(P<0.05,P<0.01),the scratch healing rate was significantly decreased(P<0.05,P<0.01),the number of migrating cells and invading cells significantly reduced(P<0.01),and the expressions of JAK2,STAT3,VEGF and HIF-1αproteins significantly decreased(P<0.05,P<0.01).Conclusion Yanghe Decoction containing serum can inhibit the proliferation,migration and invasion of BT-549 cells intervened by CAAcm,and the mechanism may be related to the inhibition of JAK2,STAT3,VEGF and HIF-1αprotein expressions.

关 键 词：阳和汤 乳腺癌 肿瘤相关脂肪细胞 迁移 侵袭 BT-549细胞 

分 类 号：R285.5[医药卫生—中药学]