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半夏泻心汤含药血清对胃癌细胞来源外泌体诱导BMSCs增殖、迁移、侵袭的影响     被引量:8

Effects of Banxia Xiexin Decoction-treated serum on the proliferation, migration and invasion of BMSCs induced by gastric cancer cells derived exosomes

文献类型:期刊文献

中文题名:半夏泻心汤含药血清对胃癌细胞来源外泌体诱导BMSCs增殖、迁移、侵袭的影响

英文题名:Effects of Banxia Xiexin Decoction-treated serum on the proliferation, migration and invasion of BMSCs induced by gastric cancer cells derived exosomes

作者:董俊刚[1];刘喜平[1];李沛清[1];王庆苗[2];朱中博[1];崔国宁[1]

第一作者:董俊刚

机构:[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]甘肃中医药大学中医临床医学院,甘肃兰州730000

第一机构:甘肃中医药大学基础医学院(敦煌医学研究所)

年份:2022

卷号:44

期号:1

起止页码:42

中文期刊名:中成药

外文期刊名:Chinese Traditional Patent Medicine

收录:CSTPCD;;北大核心:【北大核心2020】;CSCD:【CSCD2021_2022】;

基金:国家自然科学基金资助项目(81860782,81860813)。

语种:中文

中文关键词:半夏泻心汤;胃癌;骨髓间充质干细胞(BMSCs);外泌体;Shh信号通路

外文关键词:Banxia Xiexin Decoction;gastric cancer;bone marrow mesenchymal stem cells(BMSCs);exosomes;Shh signaling pathway

摘要:目的探讨半夏泻心汤对胃癌细胞来源外泌体诱导骨髓间充质干细胞(BMSCs)增殖、迁移、侵袭的影响。方法荧光染料1,1′-双十八烷基-3,3,3′,3′-四甲基吲哚羰花青高氯酸盐(Dil)标记胃癌细胞来源外泌体,制备半夏泻心汤含药血清。实验分为空白组,模型组,半夏泻心汤低、中、高剂量组及Shh阻断剂组,各组上室加入BMSCs细胞悬液,下室加入无外泌体血清的培养基,除空白组外其他各组下室加入胃癌细胞来源外泌体,模型组及空白组上室加入含10%正常对照血清,半夏泻心汤低、中、高剂量组上室内加入含10%半夏泻心汤低、中、高剂量含药血清,Shh阻断剂组上室加入含20μmol/L GANT61(Shh信号通路阻断剂)的10%空白血清。激光共聚焦显微镜观察BMSCs对胃癌细胞来源外泌体的摄取,MTT法检测各组BMSCs增殖率,Transwell小室检测BMSCs迁移、侵袭能力,Western blot检测Shh、Ptch1、Smo、Gli1、c-Myc蛋白表达。结果与空白组比较,模型组BMSCs内红色荧光标记平均光密度值(MOD)、细胞增殖率、细胞迁移、侵袭能力及Shh、Ptch1、Smo、Gli1、c-Myc蛋白表达升高(P<0.05),半夏泻心汤各剂量组各指标均下降,以高剂量组更明显(P<0.05)。结论半夏泻心汤可干预BMSCs对胃癌细胞来源外泌体的摄取,下调c-Myc蛋白及Shh信号通路Shh、Ptch1、Smo、Gli1蛋白表达,抑制胃癌细胞来源外泌体诱导的BMSCs增殖、迁移、侵袭。
AIM To investigate the effects of Banxia Xiexin Decoction on the proliferation, migration and invasion of bone marrow mesenchymal stem cells(BMSCs) induced by gastric cancer cells derived exosomes.METHODS The fluorescent dye Dil was used to label gastric cancer cells derived exosomes;the serum containing Banxia Xiexin Decoction was prepared. The experiment was divided into blank group, model group, groups for intervention of low dose, medium dose and high dose of Banxia Xiexin Decoction, and positive group with the use of Shh signal pathway blocker. Various groups had their lower chamber added with exosome-free medium and later gastric cancer cells derived exosomes except for the blank group. The upper chambers were added with BMSCs suspension, and later 10% normal control serum in the model group and blank group;10% serum containing low, medium and high dose of Banxia Xiexin Decoction in the three different decoction groups;and 10% blank serum containing 20 μmol/L GANT61(Shh signal pathway blocker) in the positive group. BMSCs had their uptake of gastric cancer cells derived exosomes observed by laser confocal microscopy;their proliferation detected by MTT method;their migration and invasion determined by Transwell chambers;their protein expressions of Shh, Ptch1,Smo, Gli1 and c-Myc investigated by Western blot.RESULTS Compared with BMSCs of the blank group, BMSCs in the model group shared increased mean optical density(MOD),cell proliferation rate, migration and invasion ability and expression levels of Shh, Ptch1,Smo, Gli1 and c-Myc protein(P<0.05). But decreased levels in the aforementioned indices were observed in Banxia Xiexin Decoction groups, especially in the high dose group(P<0.05).CONCLUSION Banxia Xiexin Decoction inhibits the proliferation, migration and invasion of BMSCs induced by gastric cancer cells derived exosomes through interference with their uptakes, down regulation of the expressions of c-Myc protein and Shh, Ptch1, Smo, and Gli1 proteins.

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