Oncotarget

Research Papers:

Brassinin inhibits STAT3 signaling pathway through modulation of PIAS-3 and SOCS-3 expression and sensitizes human lung cancer xenograft in nude mice to paclitaxel

Jong Hyun Lee, Chulwon Kim, Gautam Sethi and Kwang Seok Ahn _

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Oncotarget. 2015; 6:6386-6405. https://doi.org/10.18632/oncotarget.3443

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Abstract

Jong Hyun Lee1, Chulwon Kim1, Gautam Sethi2 and Kwang Seok Ahn1

1 College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul, Republic of Korea

2 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Correspondence to:

Gautam Sethi, email:

Kwang Seok Ahn, email:

Keywords: Brassinin, STAT3, PIAS-3, SOCS-3, apoptosis

Received: December 16, 2014 Accepted: January 21, 2015 Published: January 31, 2015

Abstract

Persistent phosphorylation of signal transducers and activators of transcription 3 (STAT3) is frequently observed in tumor cells. We found that brassinin (BSN) suppressed both constitutive and IL-6-inducible STAT3 activation in lung cancer cells. Moreover, BSN induced PIAS-3 protein and mRNA, whereas the expression of SOCS-3 was reduced. Knockdown of PIAS-3 by small interfering RNA prevented inhibition of STAT3 and cytotoxicity by BSN. Overexpression of SOCS-3 in BSN-treated cells increased STAT3 phosphorylation and cell viability. BSN down-regulated STAT3-regulated gene products, inhibited proliferation, invasion, as well as induced apoptosis. Most importantly, when administered intraperitoneally, combination of BSN and paclitaxel significantly decreased the tumor development in a xenograft lung cancer mouse model associated with down-modulation of phospho-STAT3, Ki-67 and CD31. We suggest that BSN inhibits STAT3 signaling through modulation of PIAS-3 and SOCS-3, thereby attenuating tumor growth and increasing sensitivity to paclitaxel.


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