RESUMO
OBJECTIVE: To investigate the efficacy of Ciji Hua'ai Baosheng formula (CHBF) on microvessel density (MVD) and vascular endothelial growth factor (VEGF), kinase insert domain-containing receptor (KDR) and basic fibroblast growth factor (bFGF) expression in serum and tumor tissue of mice receiving chemotherapy for the treatment of H(22) hepatocellular carcinoma. METHODS: Sixty Kunming mice were injected subcutaneously with H(22) hepatoma carcinoma cell suspensions into the right anterior armpit. Seven days later, all transplanted tumor were formed and the mice were intraperitoneally injected 200 mg/kg Cytoxan (CTX) to establish the models of tumor-bearing mouse chemotherapy, then they were randomly divided into model group, continuing CTX chemotherapy group (CTX group), and three CHBF (117, 58.5 and 29.25 g/kg) groups. After ten days of treatments, histology was observed, contents of VEGF, KDR and bFGF in serum and tumor tissue were measured by enzyme-linked immunosorbent assay (ELISA), VEGF and bFGF protein expression and MVD tagged by CD34 were detected by immunohistochemistry. RESULTS: MVD in CHBF (117, 58.5 g/kg) and CTX groups was significantly lower than that in model group (P < 0.01); expressions of VEGF, KDR and bFGF in serum and tumor tissue in CHBF (117 g/kg) group were less than those in model group (P < 0.05; P < 0.01); the expressions of MVD, VEGF and bFGF in tumor tissue of CHBF (117 g/kg) group were also less than those in CTX group (P < 0.05; P < 0.01). CONCLUSION: CHBF can effectively reduce the expression of VEGF, KDR and bFGF in serum and tumor tissue, and decrease MVD and delay tumor progression.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Feminino , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Ciji-Hua'ai-Baosheng Decoction (CHBD) is a traditional Chinese formula that may attenuate the toxicity and side-effects of chemotherapy. The formula may also prolong the life of cancer patients. Whether CHBD should be employed as adjunctive therapy for cancer patients receiving chemotherapy has yet to be determined as does the mechanism whereby CHBD exerts its beneficial effects. AIM OF THE STUDY: To document the potential effects of CHBD on tumor growth and immune function in a murine model of hepatocellular carcinoma (HCC) receiving chemotherapy. MATERIALS AND METHODS: Sixty Kunming mice were injected subcutaneously with H22 hepatoma cells in the right anterior armpit. After seven days, the mice with formed tumors were injected with Cytoxan (CTX) (200â¯mg/kg) to establish the chemotherapy model. These mice were randomly divided into 5â¯groups: model (untreated controls), control (CTX,33.33â¯mg/kg), and high CHBD (H) (117â¯g/kg), moderate CHBD (M) (58.5â¯g/kg) and low CHBD (L) (29.25â¯g/kg) treated groups. Tumor weights and inhibitory ratio (decrease in tumor dimensions), histology of tumor, colon, spleen and liver, and biochemical tests of liver and kidney function were documented after 10 days. Serum and tumor IL-2, IFN-γ, IL-6, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA) and Western blot respectively. The potential bioactive compounds in CHBD were characterized by UHPLC-MS. RESULTS: Although tumor weights were decreased in CTX alone and CHBD (H) and CHBD (M) groups (-66%, -41% and -25% respectively), tumor cell density was reduced to the greatest extent in the CHBD (H) group. CHBD had no evident effects on liver and kidney function. CTX-induced colon inflammation and decrease in spleen lymphocytes were attenuated with CHBD treatment. CHBD increased serum IL-2, IFN-γ and TNF-α, but decreased IL-6 levels in serum and tumor tissue. UHPLC-MS analysis of CHBD revealed the presence of 11 bioactive compounds. CONCLUSIONS: In this murine model of HCC receiving chemotherapy, CHBD inhibited tumor growth, improved immune function and pro-inflammatory cytokine responses while attenuating CTX-associated side effects.