Antitumor Effect And Mechanism Of Aciton Of Sesquiterpenoids From Panax Ginseng

Ginseng is a plant of the genus Araliaceae.It is a valuable Chinese herbal medicine in China,which has the effect in improving the body's immunity.So it is often used as tonic.According to the literature,it can be knowed that ginseng has a variety of active ingredients,most of which are saponins and polysaccharide,and they all have a wide range of pharmacological activities,which mainly in the central nervous system,cerebrovascular and anti-tumor.However,there are few studies on fat-soluble components.In order to use the active ingredients of ginseng more effectively,this paper was aimed to study the anti-tumor activity of sesquiterpenoids from Panax ginseng?SPG?systematically,and its related mechanism of action in further,at the same time,to study the myelosuppression induced by 5-FU in the anti-tumor process.The research results and contents as follows:?1?Anti-tumor effect and mechanism of action of SPG on H₂₂ tumor-bearing miceThe H₂₂ tumor-bearing mice were established,After 14 days treatment,the eyeballs were removed,and the tumor tissues and organ were excised and weighed.The tumor inhibition rate and organ indexes were calculated.The serum aspartate aminotransferase?AST?,alanine aminotransferase?ALT?and urea nitrogen?BUN?in the serum of tumor-bearing mice were detected.At the same time,the levels of tumor necrosis factor-??TNF-??,?-interferon?IFN-??,interleukin-2?IL-2?,interleukin-3?IL-3?,vascular endothelial growth factor?VEGF?were detected,H&E staining was used to observe the pathological changes of spleen tissue and tumor tissue.The expressiones of tumor tissue protein of tumor-bearing mice was determined by Western blotting.The anti-tumor activity and mechanism of ginseng were analyzed by the above results.The results showed that SPG can effectively inhibit growth of tumor,and the tumor inhibition rate can reach 65.92%in high dose of SPG group,the tumor inhibition rate can reach 83.70%in 5-FU combined with high dose of SPG.Compare with mode group the levels of AST,ALT,BUN and VEGF in serum of tumor-bearing mice were significantly decreased,and the levels of IL-2,IL-3,TNF-?and INF-?were significantly increased.Compared with the model group,tomur tissue of mice in the 5-FU combined with SPG groups were showed a large area of tumor necrosis.The results of western blot showed that SPG can inhibit the expressiones of Bcl-2 and VEGF of tumor tissues,and regulate P38MAPK protein channel to inhibit the growth of tumor tissue.compare with 5-FU group,SPG improved the levels of TGF-?,EPO and GM-CSF in the serum of tumor-bearing mice significantly,which proved that SPG can relieve the myelosuppressive effect of 5-FU in the process of tumor-bearing mice.Conclusion:SPG had significant anti-tumor activity,and SPG combined with5-FU in the anti-tumor process can improved action of anti-tumor,and reduced the myelosuppressive effect of 5-FU.Its anti-tumor mechanism may be related to down-regulation the expressiones of Bcl-2 and VEGF,as well as regulation of P38MAPK protein channels.?2?Antitumor effect and mechanism of aciton of SPG on S₁₈₀ tumor-bearing miceFirstly,to establish the S180 tumor-bearing mouse.The weight,tumor inhibition rate and organ index of tumor-bearing mice were determined.The levels of serum alanine aminotransferase?ALT?and aspartate aminotransferase?AST?,blood urea nitrogen?BUN?,interleukin-2?IL-2?,tumor necrosis growth factor-??TNF-??and vascular endothelial growth factor?VEGF?were detected.Pathological changes of tumor tissues of mice were observed by H&E staining in each group,the level of anti-apoptotic factors?Bcl-2?,vascular endothelial growth factor?VEGF?,p38 against mitogen-activated protein kinase?p38MAPK?and p38 mitogen-activated protein kinase phosphorylation?p-p38MAPK?protein in tumor tissues were detected by Western Blot.At the same time,the levels of transforming growth factor?TGF-??,interleukin-6?IL-6?,interleukin-4?IL-4?,granulocyte-macrophage colony-stimulating factor?GM-CSF?and erythropoietin?EPO?in bone marrow serum of tumor-bearing mice were detected.By analyzing the above results,which showed that with the increase of SPG dose,the tumor inhibition rate increased significantly.The inhibition rate of high-dose SPG group was 76.29%,and the inhibition rate of 5-FU combined with high-SPG group was 85.92%.Compared with the model group,the levels of IL-2and TNF-?in the serum of SPG groups and the co-administered group were significantly increased,and the levels of ALT,AST,BUN and VEGF were significantly decreased.H&E staining showed that the cells in the model group were arranged neatly and closely,and a large number of nuclei were observed,and the growth state was good.The number of nuclei of tumor tissues in the SPG groups was reduced significantly,however,it can be seen that the arrangement was loose and a large area of necrosis occurred in the combined group.The results of western Blot showed that the levels of Bcl-2 and VEGF protein in the tumor tissues of the combined administration group were significantly decreased relative to the model group,but the level of p-p38MAPK was significantly increased.The level of GM-CSF was increased of serum in mice in the 5-FU combined with SPG group significantly,which indeced that SPG can relieve the myelosuppressive effect of 5-FU in the anti-tumor process.Conclusion:SPG had significant anti-tumor activity,and SPG combined with 5-FU in the anti-tumor process can improved action of anti-tumor,and relieve the myelosuppressive effect of 5-FU in the anti-tumor process.Its anti-tumor mechanism may be related to regulate the P38MAPK protein channels.