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Hedyotis diffusa Willd Inhibits Colorectal Cancer Growth in Vivo via Inhibition of STAT3 Signaling Pathway
Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, 1 Huatuo Road, Minhou Shangjie, Fuzhou 350108, China
Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, 1 Huatuo Road, Minhou Shangjie, Fuzhou 350108, China
Department of Pharmacology, Fujian University of Traditional Chinese Medicine, 1 Huatuo Road, Minhou Shangjie, Fuzhou 350108, China
* Author to whom correspondence should be addressed.
Received: 28 March 2012; in revised form: 3 May 2012 / Accepted: 10 May 2012 / Published: 18 May 2012
Abstract: Signal Transducer and Activator of Transcription 3 (STAT3), a common oncogenic mediator, is constitutively activated in many types of human cancers; therefore it is a major focus in the development of novel anti-cancer agents. Hedyotis diffusa Willd has been used as a major component in several Chinese medicine formulas for the clinical treatment of colorectal cancer (CRC). However, the precise mechanism of its anti-tumor activity remains largely unclear. Using a CRC mouse xenograft model, in the present study we evaluated the effect of the ethanol extract of Hedyotis diffusa Willd (EEHDW) on tumor growth in vivo and investigated the underlying molecular mechanisms. We found that EEHDW reduced tumor volume and tumor weight, but had no effect on body weight gain in CRC mice, demonstrating that EEHDW can inhibit CRC growth in vivo without apparent adverse effect. In addition, EEHDW treatment suppressed STAT3 phosphorylation in tumor tissues, which in turn resulted in the promotion of cancer cell apoptosis and inhibition of proliferation. Moreover, EEHDW treatment altered the expression pattern of several important target genes of the STAT3 signaling pathway, i.e., decreased expression of Cyclin D1, CDK4 and Bcl-2 as well as up-regulated p21 and Bax. These results suggest that suppression of the STAT3 pathway might be one of the mechanisms by which EEHDW treats colorectal cancer.
Keywords: Hedyotis diffusa Willd; Chinese medicine; colorectal cancer; STAT3 pathway; apoptosis; proliferation
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MDPI and ACS Style
Cai, Q.; Lin, J.; Wei, L.; Zhang, L.; Wang, L.; Zhan, Y.; Zeng, J.; Xu, W.; Shen, A.; Hong, Z.; Peng, J. Hedyotis diffusa Willd Inhibits Colorectal Cancer Growth in Vivo via Inhibition of STAT3 Signaling Pathway. Int. J. Mol. Sci. 2012, 13, 6117-6128.
Cai Q, Lin J, Wei L, Zhang L, Wang L, Zhan Y, Zeng J, Xu W, Shen A, Hong Z, Peng J. Hedyotis diffusa Willd Inhibits Colorectal Cancer Growth in Vivo via Inhibition of STAT3 Signaling Pathway. International Journal of Molecular Sciences. 2012; 13(5):6117-6128.
Cai, Qiaoyan; Lin, Jiumao; Wei, Lihui; Zhang, Ling; Wang, Lili; Zhan, Youzhi; Zeng, Jianwei; Xu, Wei; Shen, Aling; Hong, Zhenfeng; Peng, Jun. 2012. "Hedyotis diffusa Willd Inhibits Colorectal Cancer Growth in Vivo via Inhibition of STAT3 Signaling Pathway." Int. J. Mol. Sci. 13, no. 5: 6117-6128.