Tenglong Buzhong granules(藤龙补中颗粒) inhibits the growth of SW620 human colon cancer in vivo

OBJECTIVE: To observe the anticancer effects of the granular preparation of Tenglong Buzhong decoction(藤龙补中汤,TBD), i.e Tenglong Buzhong granules(藤龙补中颗粒, TBG), in human SW620 colon cancer. METHODS: BALB/c nude mice were subcutaneously transplanted with SW620 cells, and treated with TBG(2.56 g/kg, once per day) and/or 5-Fu(104 mg/kg, once per week) for 21 d. Apoptosis, Caspase activities and cellular senescence were measured by commercial kits. The protein expression and phosphorylation were detected by Western blot or immunohistochemistry. RESULTS: TBG and 5-Fu inhibited tumor growth. The tumor inhibition rate of the TBG, 5-Fu, and TBG+5-Fu groups was 42.25%, 51.58%, and 76.08%, respectively. Combination of TBG and 5-Fu showed synergetic anticancer effects. TBG and 5-Fu induced apoptosis, activated caspase-3,-8, and-9, increased SMAC expression, inhibited XIAP expression. TBG induced cellular senescence, upregulated cyclin-dependent kinase inhibitor 1a(CDKN1a) and cyclin-dependent kinase inhibitor 2a(CDKN2a) expression, and inhibited phosphorylation of retinoblastoma-associated protein(RB) and expression of cyclin E1(CCNE1) and cyclindependent kinases(CDK) 2. TBG also inhibited angiogenesis accompanied by downregulation of vascular endothelial growth factor(VEGF) and hypoxiainducible factor-1α(HIF-1α). CONCLUSIONS: TBG inhibits SW620 colon cancer growth, induces apoptosis via SMAC-XIAP-Caspases signaling, induces cellular senescence through CDKN1a/CDKN2a-RB-E2F signaling, inhibits angiogenesis by down-regulation of HIF-1α and VEGF, and enhances the effects of 5-Fu.