Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts.
Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts.
复制标题
黄芪甲苷抑制胃癌相关成纤维细胞的病理功能
DOI：
10.3748/wjg.v23.i48.8512
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发表时间：
2017-12-28
影响因子：
4.3
通讯作者：
Lu HW
中科院分区：
文献类型：
--
作者：
Wang ZF;Ma DG;Zhu Z;Mu YP;Yang YY;Feng L;Yang H;Liang JQ;Liu YY;Liu L;Lu HW
AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts, and to explore the underlying mechanism. METHODS Paired gastric normal fibroblast (GNF) and gastric cancer-associated fibroblast (GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside IV. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs, and astragaloside IV-treated GCAFs, and used to culture BGC-823 human gastric cancer cells. Proliferation, migration and invasion capacities of BGC-823 cells were determined by MTT, wound healing, and Transwell invasion assays, respectively. The action mechanism of astragaloside IV was investigated by detecting the expression of microRNAs and the expression and secretion of the oncogenic factor, macrophage colony-stimulating factor (M-CSF), and the tumor suppressive factor, tissue inhibitor of metalloproteinase 2 (TIMP2), in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined. RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation, migration, and invasion than GNFs (P < 0.01). Astragaloside IV treatment strongly inhibited the proliferation-, migration- and invasion-promoting capacities of GCAFs (P < 0.05 for 10 μmol/L, P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs, GCAFs expressed a lower level of microRNA-214 (P < 0.01) and a higher level of microRNA-301a (P < 0.01). Astragaloside IV treatment significantly up-regulated microRNA-214 expression (P < 0.01) and down-regulated microRNA-301a expression (P < 0.01) in GCAFs. Reestablishing the microRNA expression balance subsequently suppressed M-CSF production (P < 0.01) and secretion (P < 0.05), and elevated TIMP2 production (P < 0.01) and secretion (P < 0.05). Consequently, the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside IV. CONCLUSION Astragaloside IV can inhibit the pathological functions of GCAFs by correcting their dysregulation of microRNA expression, and it is promisingly a potent therapeutic agent regulating tumor microenvironment.
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通过数字全息显微镜在体外对伤口愈合的无定量染色和连续多模式监测。
影响因子：
3.7
作者：
Bettenworth D;Lenz P;Krausewitz P;Brückner M;Ketelhut S;Domagk D;Kemper B
通讯作者：
Kemper B
影响因子：
4
作者：
Radisky ES;Raeeszadeh-Sarmazdeh M;Radisky DC
通讯作者：
Radisky DC
影响因子：
3.9
作者：
Liao CP;Chen LY;Luethy A;Kim Y;Kani K;MacLeod AR;Gross ME
通讯作者：
Gross ME
影响因子：
4.2
作者：
Chan, Wing-Sai;Durairajan, Siva Sundara Kumar;Li, Min
通讯作者：
Li, Min
影响因子：
3.6
作者：
Narra, Kalyani;Mullins, Stefanie R.;Cheng, Jonathan D.
通讯作者：
Cheng, Jonathan D.