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

摘要

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.