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 nu...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.展开更多
OBJECTIVE: To observe the effect of Yanggan Jiedu Sanjie(YGJDSJ) formula on human hepatocellular carcinoma Bel-7402 cells.METHODS: Bel-7402 cells were treated with YGJDSJ. Cell proliferation was detected by cell count...OBJECTIVE: To observe the effect of Yanggan Jiedu Sanjie(YGJDSJ) formula on human hepatocellular carcinoma Bel-7402 cells.METHODS: Bel-7402 cells were treated with YGJDSJ. Cell proliferation was detected by cell counting kit-8 assay. Cell apoptosis was identified by Hoechst 33258 staining and flow cytometric analysis. Cell cycle distribution was quantified by flow cytometric analysis. Caspase activities were measured by commercial kit. Cell senescence was detected by senescence-associated β-galactosidase(SA-β-gal)staining. Protein expression and phosphorylation were identified by Western blot. Protein expression was knocked-down by siRNA.RESULTS: YGJDSJ inhibited proliferation of Bel-7402 cells in a dose-and time-dependent manner.YGJDSJ induced apoptosis and activated caspase-3, 8, and 9 in Bel-7402 cells. YGJDSJ-induced apoptosis was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. YGJDSJ also induced cell senescence, up-regulated cyclin-dependent kinase inhibitor 1 a(CDKN1 a) and CDKN2 a expression and down-regulated retinoblastoma protein(RB) phosphorylation in Bel-7402 cells. Specific knockdown of CDKN1 a and CDKN2 a significantly reduced YGJDSJ-induce cell senescence in Bel-7402 cells.CONCLUSION: YGJDSJ inhibited cell proliferation,induced caspase-dependent apoptosis and CDKN1 a/CDKN2 a-RB signalling mediated cell senescence in Bel-7402 cells. Our findings suggest that YGJDSJ might be potential for hepatocellular carcinoma treatment.展开更多
基金Supported by Natural Science Foundation of Shanghai Municipality:Tenglong Buzhong Decoction Inhibiting Metastasis of Colorectal Cancer by Regulation of HIF-1 α/LOX/PTK2 Signal Transduction (No. 20ZR1458700)Program from Science and Technology Commission of Shanghai Municipality:Real World Study of Tenglong Buzhong Decoction on Colorectal Cancer Metastasis and Circulating miRNAs (No. 19401933400)。
文摘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.
基金Key Basic Research Program from Science&Technology Commission of Shanghai Municipality(No.09JC1413600)Program from Science&Technology Commission of Shanghai Municipality(No.16401902500)Three-year Action Program of Shanghai Municipality for Traditional Chinese Medicine(No.ZY3-CCCX-3-3025)
文摘OBJECTIVE: To observe the effect of Yanggan Jiedu Sanjie(YGJDSJ) formula on human hepatocellular carcinoma Bel-7402 cells.METHODS: Bel-7402 cells were treated with YGJDSJ. Cell proliferation was detected by cell counting kit-8 assay. Cell apoptosis was identified by Hoechst 33258 staining and flow cytometric analysis. Cell cycle distribution was quantified by flow cytometric analysis. Caspase activities were measured by commercial kit. Cell senescence was detected by senescence-associated β-galactosidase(SA-β-gal)staining. Protein expression and phosphorylation were identified by Western blot. Protein expression was knocked-down by siRNA.RESULTS: YGJDSJ inhibited proliferation of Bel-7402 cells in a dose-and time-dependent manner.YGJDSJ induced apoptosis and activated caspase-3, 8, and 9 in Bel-7402 cells. YGJDSJ-induced apoptosis was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. YGJDSJ also induced cell senescence, up-regulated cyclin-dependent kinase inhibitor 1 a(CDKN1 a) and CDKN2 a expression and down-regulated retinoblastoma protein(RB) phosphorylation in Bel-7402 cells. Specific knockdown of CDKN1 a and CDKN2 a significantly reduced YGJDSJ-induce cell senescence in Bel-7402 cells.CONCLUSION: YGJDSJ inhibited cell proliferation,induced caspase-dependent apoptosis and CDKN1 a/CDKN2 a-RB signalling mediated cell senescence in Bel-7402 cells. Our findings suggest that YGJDSJ might be potential for hepatocellular carcinoma treatment.
