Study On Mechanism Of Anti-tumor Effect By Ginsenoside Rg3

Ginsenoside Rg3 is a kind of effective chemical component extracted tracely from the red Panix with molecular formula C42H72O13 and molecular weight 784.30 dalton. Many studies have shown that Ginsenoside Rg3 can decrease toxicity, improve symptoms of Qi –deficiency, increase immune function, and inhibit proliferation, infiltration and metastasis of the tumor cells. The etiology and development of tumor is very complicated, in which many related protein factors, some metastatic routes, as well as molecular mechanism are involved. The study of mechanism on anti-tumor effect of Ginsenoside Rg3 is now one of the attracting fields.The study includes: (1) By establishing the lymph-route metastatic model with high- potential metastatic tumor cell strain, Hca-F25//6A3-F(F), we observed the effect of Ginsenoside Rg3 on inhibiting proliferation and metastasis; analyzed the expression of metastasis related factors such as PNCA, P16 and MMPs by immunohistochemical assay (ICH) in order to study the molecular mechanism of Ginsenoside Rg3 in anti-lymphatic metastasis; moreover, the apoptosis analysis was undergone to evaluate its role of anti-tumor by light microscope, electronic microscope, and flow cytometry. (2) Using the lung metastasis mouse model implanted with RI-transgene B16 melanoma, we explored the anti-angiogenesis and the interaction of Ginsenoside Rg3 and RI by observing the inhibition of proliferation, invasion, and metastasis. (3) In vitro experiment of B16 melanoma cell line, we studied the gene and protein expression levels of Caspase-3 which is a key protease in apoptosis pathway by RT-PCR and IHC in order to explain the apoptosis mechanism induced by Ginsenoside Rg3. (4) We observed the quality of life and immune function of the breast cancer patients in chemotherapy while treated with Ginsenoside Rg3.The results showed that (1) in the lymph-route metastatic model experiment, Ginsenoside Rg3 could inhibit the growth and metastasis of tumor by increasing the expression level of p16, whereas decreasing those of PCNA and MMP-9 significantly compared with that of saline group in primary tumor tissue (P<0.001).The morphologic change showed that typical apoptic peak and more apoptosis micorobodies appeared in Ginsenoside Rg3 pretreatment and Ginsenoside Rg3 treatment groups compared with those of the other groups; (2) In the lung metastatic mouse model implanted with RI- transgene B16 melanoma, both Rg3 and RI could decrease the weight of lungs, with Rg3/RI group showing the greatest decrement among all other groups, the less extent for Rg3 and RI groups, which were significantly different from those of the W and B groups (P(0. 01).The lifespan of tumor- bearing mouse was shortened in W and B groups, with all animal dead at the 26th day of the experiment, while all mouse being alive during one and half month period of observation in Rg3/RI group. The microvessel density decreased among Rg3 and /or RI administrated groups, which showing consensus results with those of the inhibitory effect mentioned above by HE staining and Ⅷ-R Ag expression by IHC analysis; (3) The proliferation test of cultured B16 melanoma indicated that there was dose-dependent effect on inducing apoptosis by Ginsenoside Rg3. The morphological observation showed that characteristic change of apoptosis under light and fluorescent microscope. The results of RT-PCR and IHC showed that the expressions of Caspase-3 gene and protein were up-regulated; (4) In the clinical observation of the breast cancer patients in chemotherapy, the symptoms of Qi-deficiency in patients of Ginsenoside Rg3 group improved significantly, which was superior to the control group(P < 0. 05 or P < 0. 001). The level of T lymphocyte subtype ratio (CD4/ CD8) increased significantly in Ginsenoside Rg3 group compared with that of the control group ( P < 0. 001) .The study suggests that Ginsenoside Rg3 has anti-tumor effect, and the anti- lymphatic role , which is related to induce tumor apoptosis with up-regulation of p16 expression and down-regulation of PCNA an...