Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts

作者：Wang, Zhen-Fei; Ma, Da-Guang; Zhu, Zhe; Mu, Yong-Ping; Yang, Yong-Yan; Feng, Li; Yang, Hao; Liang, Jun-Qing; Liu, Yong-Yan; Liu, Li; Lu, Hai-Wen^*

来源：World Journal of Gastroenterology, 2017, 23(48): 8512-8525.

DOI：10.3748/wjg.v23.i48.8512

• Astragaloside IV
• Gastric cancer-associated fibroblasts
• Proliferation
• Migration
• Invasion
• MicroRNA

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.. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs, and astragaloside.-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. was investigated by detecting the expression of microRNAs and the expression and secretion of the oncogenic factor, macrophage colonystimulating 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. treatment strongly inhibited the proliferation-, migration-and invasion-promoting capacities of GCAFs (P < 0.05 for 10 mu mol/L, P < 0.01 for 20 mu mol/L and 40 mu mol/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. treatment significantly upregulated 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. 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.

• 出版日期2017-12-28
• 单位内蒙古医科大学