Tectorigenin ablates the inflammation-induced epithelial-mesenchymal transition in a co-culture model of human lung carcinoma

被引：22

作者：

Amin, Asif ^{[1
]}

Mokhdomi, Taseem A. ^{[1
]}

Bukhari, Shoiab ^{[1
]}

Wani, Sajad H. ^{[1
]}

Wafai, Asrar H. ^{[1
]}

Lone, Ghulam Nabi ^{[2
]}

Qadri, Ayub ^{[3
]}

Qadri, Raies A. ^{[1
]}

机构：

[1] Univ Kashmir, Dept Biotechnol, Srinagar 190006, Jammu & Kashmir, India

[2] Sherikashmir Inst Med Sci, Dept Cardiovasc & Thorac Surg, Srinagar, Jammu & Kashmir, India

[3] Natl Inst Immunol, Hybridoma Lab, New Delhi 110067, India

来源：

PHARMACOLOGICAL REPORTS | 2015年 / 67卷 / 02期

关键词：

Tectorigenin; Co-culture model; E-cadherin; Snail; E-CADHERIN EXPRESSION; REPRESSES E-CADHERIN; NF-KAPPA-B; RAW; 264.7; CANCER; SNAIL; PROGRESSION; TECTORIDIN; CELLS; GENE;

D O I：

10.1016/j.pharep.2014.10.020

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Objectives: Tumors not only manage to escape from the host immune system, but they effectively contrive to benefit from infiltrating immune cells by modifying their functions so as to create a proinflammatory microenvironment favorable for tumor progression and metastasis. In this study we investigated if tectorigenin could suppress lung cancer-induced pro-inflammatory response generated from monocytes. Materials and methods: A549:THP1 co-culture model was set-up favoring release of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha). Effect of tectorigenin on A549 imparted invasive phenotype of A549:THP-1 co-culture was monitored by cytokine release from monocytes, and metastasis/epithelial-mesenchymal transitiom (EMT) in A549 cells. Results: In a contact A549:THP1 co-culture model, THP-1 cells were activated by A549 cells favoring secretion of pro-inflammatory cytokines, TNF-alpha and IL-6. However, priming of A549 cells with tectorigenin for 24 h repressed A549 cell-induced secretion of TNF-alpha and IL-6 by THP-1 cells. Tectorigenin induced change in functional phenotype of A549 cells rendered THP-1 cells non-responsive for the secretion of IL-6 and TNF-alpha in a contact co-culture setup. Additionally, conditioned media from this non-responsive A549:THP-1 co-culture suppressed metastatic potential of A549 cells as confirmed by the wound healing and transwell migration assays. These finding were further corroborated by decrease in expression of Snail with a concomitant increase in E-cadherin, the two signature markers of EMT. Conclusion: These results clearly demonstrate the therapeutic potential of tectorigenin to prevent lung cancer elicited inflammatory and pro-metastatic response in monocytes and warrants further investigations to elucidate its mechanism of action. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

引用

页码：382 / 387

页数：6

共 32 条

[1]

The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells [J].