Studies On Anti-tumor Effect And Correlated Mechanisms Of 20(r)-ginsenoside Rg3 In Human Lung Adenocarcinoma Cells

Objective:To explore the anti-tumor effect and mechanisms of 20(R)-ginsenoside Rg3 on human lung adenocarcinoma cell line A549/DDP in vivo and in vitro.Methods:The apoptosis was analyzed by Hoechst33258 staining method and TUNEL method, and cell cycle was determined by flow cytometry (FCM). MTT was applied to determine the chemosensitivity of A549/DDP to cisplatin. cell membrane lipid fluidity was determined to observe the Rg3 effect to cell chemosensitivity, cell invasion assay was applied to determine the invasion and metastasis change of Rg3 to cell, the protein expression levels of cyclinD1, P21, P27, caspase-3, caspasse-8, nm23, and LRP were determined by Western blotting analyses. The subcutaneous transplantable tumor model of human lung adenocarcinoma in nude mice was established to observe anti-tumor effect of Rg3 in vivo.Results:The typical apoptosis appearance was induced and the cell cycle was arrested at G0/G1 phase; Rg3 could make the IC50 and drug-resistant index of cisplatin decrease; cell membrane lipid fluidity was decreased; cell invasion ability decreased; anti-tumor effect of Rg3 was dose-dependent; expression of cyclinD1 were down-regulated, P21, P27, caspase-3 and caspase-8 expression was up-regulated; expression of nm23 were upregulated, and LRP expression had no obvious change. In vivo, Rg3 could obviously inhibit the growth of transplanted tumor.Conclusions:1,20(R)-ginsenoside Rg3 could inhibit the growth of A549/DDP cells by inhibiting the cells proliferation and promoting apoptosis;2,The mechanism of apoptosis maybe correlated with up-regulation of caspase-3 and caspase-8;3,The mechanism of the inhibition of cells proliferation maybe correlated with down-regulation of cyclinD1 and up-regulation of P21 and P27;4,20(R)-ginsenoside Rg3 can restrain A549/DDP cell invasion and metastasis, and it may have relationship with the upregulation of nm23;5,20(R)-ginsenoside Rg3 can enhance the A549/DDP cell chemosensitivity to cisplatin, and it may have relationship with the upregulation of caspase-3 and the cell membrane lipid fluidity decreased;6,In vivo,20(R)-ginsenoside Rg3 associated with chemotherapeutics will present the best anti-tumor effect, and can decrease the toxicity and adverse effect of chemotherapeutics.