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Herbal extract “Songyou Yin” inhibits tumor growth and prolongs survival in nude mice bearing human hepatocellular carcinoma xenograft with high metastatic potential

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Abstract

Purpose

Chinese herbs have become a focus of interest in cancer treatment. This study evaluates the effect of the herbal compound extract “Songyou Yin” (containing Salvia miltiorrhiza Bge.-danshen and other four herbs) on hepatocellular carcinoma (HCC).

Methods

Human HCC cell line MHCC97H with high-metastatic potential was employed for in vitro study. In vivo study was conducted in nude mice bearing HCC orthotopic xenograft with MHCC97H.

Results

In vitro, “Songyou Yin” caused dramatic attenuation of tumor proliferation by induction of apoptosis that was associated with caspase-3 activation, and inhibit invasiveness of MHCC97H via reducing matrix metalloproteinase-2 (MMP2) activity. In vivo, “Songyou Yin” minimized cancer-related body weight loss of mice bearing tumors without distinct toxicity, and inhibited tumor growth with stepwise increased dosage of “Songyou Yin” and accorded with the expression of proliferating cell nuclear antigen. Moreover, “Songyou Yin” inhibited tumor growth was associated with an increased TUNEL-positive apoptosis as well as a decreased microvessel density and vascular endothelial growth factor (VEGF) abundance, and inhibited tumor invasion via down-regulation of MMP2. The lung metastatic extent was decreased (p < 0.01, compared with control). The life span of nude mice bearing xenografts was 75.0 ± 3.9 days in “Songyou Yin” group, whereas it was 52.0 ± 2.3 days in the control (p < 0.001).

Conclusions

Nontoxic herbal compound extract “Songyou Yin” inhibited tumor growth and prolonged survival, via inducing apoptosis and down-regulation of MMP2 and VEGF, which indicated its potential use in patients with advanced HCC.

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Acknowledgments

We thank Yuan Ji, MD, PhD, and Teng-Fang Zhu for their expertise in immunohistochemistry; we thank Peng Shi for his assistance in data analysis. This work was partially supported by the State Key Basic Research Program of China grant 2004CB518700, and Foundation of Key Laboratory of Carcinogenesis and Cancer Invasion Grant, Fudan University, Ministry of Education, China.

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Authors and Affiliations

  1. Department of General Surgery, The 6th People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, 200233, China

    Xiu-Yan Huang & Qi Zheng

  2. Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, China

    Lu Wang, Qi-Song Li & Zhao-You Tang

  3. Department of Neurology, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, China

    Zi-Li Huang

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  1. Xiu-Yan Huang
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  2. Lu Wang
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  5. Qi-Song Li
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Correspondence to Zhao-You Tang.

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Huang, XY., Wang, L., Huang, ZL. et al. Herbal extract “Songyou Yin” inhibits tumor growth and prolongs survival in nude mice bearing human hepatocellular carcinoma xenograft with high metastatic potential. J Cancer Res Clin Oncol 135, 1245–1255 (2009). https://doi.org/10.1007/s00432-009-0566-8

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