Investigation of the anti-cancer effect of quercetin on HepG2 cells in vivo.

Jin Zhou,Zhujuan Xiong,Lin Li,Wenxiu Yao,Li Fang,Jiaxu Liao,Xiang Zhou,Fabrizio Mattei

doi:10.1371/journal.pone.0172838

Abstract

Quercetin, a natural polyphenolic flavonoid compound, can inhibit the growth of several malignant cancers. However, the mechanism still remains unclear. Our previous findings have suggested that quercetin can significantly inhibit HepG2 cell proliferation and induce cell apoptosis in vitro. It can also affect cell cycle distribution and significantly decrease cyclin D1 expression. In this study, we investigated the anti-cancer effect of quercetin on HepG2 tumor-bearing nude mice and its effect on cyclin D1 expression in the tumor tissue. First, the nude murine tumor model was established by subcutaneous inoculation of HepG2 cells, then quercetin was administered intraperitoneally, and the mice injected with saline solution were used as controls. The daily behavior of the tumor-bearing mice was observed and differences in tumor growth and survival rate were monitored. The expression of cyclin D1 in isolated tumor sections was evaluated by immunohistochemistry. We found that HepG2 tumor became palpable in the mice one-week post-inoculation. Tumors in the control group grew rapidly and the daily behavior of the mice changed significantly, including listlessness, poor feeding and ataxia. The mice in quercetin-treated group showed delayed tumor growth, no significant changes in daily behavior, and the survival rate was significantly improved. Finally, we observed increased tumor necrosis and a lighter cyclin D1 staining with reduced staining areas. Our findings thus suggest that quercetin can significantly inhibit HepG2 cell proliferation, and this effect may be achieved through the regulation of cyclin D1 expression.

Highlights

Hepatic cancer is one of the most common malignant cancers in China and it seriously threatens people’s health
The onset of hepatic cancer is usually occult and difficult to be diagnosed at the early stage, but it grows rapidly and shows the high rate of metastasis
Compared to the control group, the mice treated with quercetin exhibited slow tumor growth rates and no significant behavioral changes

Summary

Introduction

Hepatic cancer is one of the most common malignant cancers in China and it seriously threatens people’s health. The onset of hepatic cancer is usually occult and difficult to be diagnosed at the early stage, but it grows rapidly and shows the high rate of metastasis. Most patients are diagnosed with hepatic cancer at the advanced stages. The most common treatments are surgery, stereotactic radiation, chemotherapy and interventional. Anti-cancer effect of quercetin in vivo embolization, as well as the recently developed targeted cancer therapy. Hepatic cancer is a polygenic disease with complex mechanism and signaling pathways, for which it is difficult to achieve a successful therapeutic effect by single treatment modality. The use of targeted agents to regulate multiple signaling pathways has emerged as a novel paradigm for hepatic cancer treatment

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Conclusion