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Open Access Highly Accessed Research article

Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts

Chi Man Tsang1, Yuk Chun Cheung1, Vivian Wai-Yan Lui2, Yim Ling Yip1, Guitao Zhang13, Victor Weitao Lin1, Kenneth Chat-Pan Cheung1, Yibin Feng4* and Sai Wah Tsao1*

Author Affiliations

1 Department of Anatomy, The University of HongKong, HongKong, SAR, China

2 Department of Otoloaryngology, University of Pittsburgh School of Medicine, Pittsburgh, USA

3 Department of Anatomy, Histology and Embryology, Capital Medical University, Beijing, China

4 School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of HongKong, HongKong, SAR, China

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BMC Cancer 2013, 13:619  doi:10.1186/1471-2407-13-619

Published: 31 December 2013

Abstract

Background

Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented.

Methods

In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models.

Results

Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R.

Conclusions

Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC.