Studies Of Antitumor Effect And Mechanisms Of Total Glucosides From Centella Asiatica

OBJECTIVE: To evaluate the antitumor effect and mechanisms of total glucosides extracted from Centella asiatca (GCA). METHODS: 1. Human hepatoma cell lines SMMC-7721 and HepG2, human leukemic monocyte lymphoma cell line U937 and human gastric cancer cell line SGC-7901 were selected to investigate the antitumor effect of GCA by MTT in vitro. The cell cycle and apoptotic rate of sensitive cell line treated with GCA were observed by flow cytometry (FCM). The protein expression of NF-κB was measured by western blotting 2. Peripheral blood mononuclear cells (PBMC) were separated from whole blood and stimulated with PHA. The effect of GCA on PBMC was measured by MTT assay. 3. Immunosuppressive model in mice was established via intraperitoneal injection of cyclophosphamide (CTX) at one time. The immunomodulatory effect of GCA was evaluated by immune organ indexes, phagocytic percentage of macrophage and quantitative hemolysis of cock red blood cells. 4. Immunosuppressive model in mice was set up by irradiation of 60Co-γray at one time. The immunomodulatory effect of GCA was evaluated by immune organ indexes, phagocytic percentage of macrophage, quantitative hemolysis of cock red blood cells, the proliferation of spleen lymphocytes and the level of IL-2 and SOD in serum. RESULTS: 1. GCA has significant antitumor effect on HepG2, but not on SGC-7901, SMMC-7721 and U937. GCA could inhibit HepG2 cell cycle at the phase of G0/G1 and induce the apoptosis at the dose of 100.0μg/ml. The expression of NF-κB protein is downregulated by GCA. 2. MTT result reveals that GCA has no effect on the proliferation of PBMC. 3. GCA could prominently enhance the thymus index, phagocytic percentage of macrophage and quantitative hemolysis of cock red blood cells in mice immunosuppressed by CTX. 4. GCA could remarkbaly enhance the thymus and spleen indexes, phagocytic percentage of macrophage, quantitative hemolysis of cock red blood cells and the proliferation of spleen lymphocytes in mice immunosuppressed byγray. GCA at dose of 50.0 mg/kg could also increase the level of IL-2 and SOD in serum. CONCLUSION: The results suggest that GCA has significant antitumor effect on HepG2. The antitumor mechanisms might be due to inducing apoptosis of cells and improving immunomodulatory effect in mice.