Antitumor activity of total flavonoids from Tetrastigma hemsleyanum Diels et Gilg is associated with the inhibition of regulatory T cells in mice

Zhengquan Feng,1,2 Wanrong Hao,3 Xiaoyang Lin,3 Daping Fan,4 Juhua Zhou5 1Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China; 2Department of Oncology, Guang An Men Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China; 3Department of Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People's Republic of China; 4Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC, USA; 5Institute for Tumor Immunology, Ludong University College of Life Sciences, Yantai, Shandong, People's Republic of China Objective: To determine the antitumor activity of Radix tetrastigmae flavonoids and their inhibitory effect on regulatory T cells (Tregs) in mice. Materials and methods: Total flavonoids were isolated from Radix tetrastigmae, the root of Tetrastigma hemsleyanum Diels et Gilg, and administered to C57BL/6 mice by oral gavage after inoculation with Lewis lung carcinoma (LLC) cells. The effects of total flavonoids on tumor growth in vivo were examined. Flow cytometry was used to study the effects on Tregs, and enzyme-linked immunosorbent assay was used to analyze the changes in the serum levels of transforming growth factor ß, prostaglandin E2, and cyclooxygenase 2 after tumor inoculation and flavonoid administration. Results: Total flavonoids from T. hemsleyanum Diels et Gilg significantly inhibited tumor growth in C57BL/6 mice inoculated with LLCs. These flavonoids dramatically suppressed regulatory T-cell development in tumor-bearing mice. Further studies revealed that total flavonoids significantly decreased the serum levels of transforming growth factor β, prostaglandin E2, and cyclooxygenase 2 in tumor-bearing mice, which may be responsible for the inhibition of Tregs. Conclusion: The antitumor activity of total flavonoids from T. hemsleyanum Diels et Gilg is associated with the inhibition of Tregs in a mouse tumor model. Total flavonoids from T. hemsleyanum Diels et Gilg may be used as antitumor agents in cancer prevention and treatment. Keywords: flavonoids, radix tetrastigmae, regulatory T cells, tumor growth, TGF-β1