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

摘要: // Jong Hyun Lee 1 , Chulwon Kim Gautam Sethi 2 and Kwang Seok Ahn College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul, Republic Korea Department Pharmacology, Yong Loo Lin School National University Singapore, Singapore Correspondence to: Sethi, email: Ahn, Keywords : Brassinin, STAT3, PIAS-3, SOCS-3, apoptosis Received December 16, 2014 Accepted January 21, 2015 Published 31, Abstract Persistent phosphorylation signal transducers activators transcription 3 (STAT3) is frequently observed in tumor cells. We found that brassinin (BSN) suppressed both constitutive IL-6-inducible STAT3 activation lung cancer Moreover, BSN induced PIAS-3 protein mRNA, whereas the expression SOCS-3 was reduced. Knockdown by small interfering RNA prevented inhibition cytotoxicity BSN. Overexpression BSN-treated cells increased cell viability. down-regulated STAT3-regulated gene products, inhibited proliferation, invasion, as well apoptosis. Most importantly, when administered intraperitoneally, combination paclitaxel significantly decreased development a xenograft mouse model associated with down-modulation phospho-STAT3, Ki-67 CD31. suggest inhibits signaling through modulation thereby attenuating growth increasing sensitivity to paclitaxel.