| Uterine cervix cancer and lung cancer are common malignant tumors all over the world. The two both threaten the human health. Surgery, radiotherapy, and chemotherapy are the three major cancer therapeutic strategies. With the development of modern cellular biology and molecular biology, apoptosis therapy by inducing apoptosis of tumor cells is considered to be a new and effective treatment. Exploration of efficient and low toxicity apoptosis inducers may be the most promising direction for antitumor drugs, natural medicine research on inducing apoptosis of tumor cells has become one of the hotspots of anticancer drug research in recent years.Ginsenoside Rh2 is one of the natural inducers of apoptosis for cancer treatment. It is a dammarane saponin derived from Panax ginseng, has been identified as the major component responsible for ginseng's antitumor action. Although accumulating evidences showed that G-Rh2 can induce apoptosis of various tumors and play broad-spectrum anti-tumor activity in vivo and in vitro, the cell signal transduction molecular mechanism of inducing apoptosis of tumor cells by G-Rh2, especially its non-organic specific antitumor effects, has not been fully elucidated. In this study we used human cervical cancer cell line HeLa and lung cancer cell line A549 as experimental subjects to study the cell cycle and related protein expression change during the apoptosis process of these cells induced by G-Rh2 and explore the molecular mechanism of G-Rh2's antitumor activity.We used MTT way to detect proliferation of HeLa cells and A549 cells treated by G-Rh2 of 0-60μM-dose for 48 hours and separately calculate the IC50 of G-Rh2. Flow cytometry (FCM) was used to detect the change of cell cycle about these two cells treated with G-Rh2 of 0-60μM-dose for 12,24,48,60 and 72 hours. Finally, Western blotting was used to analyze the expression of correlative protein ERa, ERP and TNFa. The results of MTT showed that the survival rate of HeLa and A549 cells were in a dose-dependent manner. The IC50 of G-Rh2 when treated HeLa is 45μM and A549 is 48μM. FCM analysis found that G-Rh2 blocked the cycle within G1 phase of these two cells in a dose-and time-dependent manner. The results of Western blotting showed that the expression of ERa was down-regulated and ERβwas up-regulated, in a dose-and time-dependent manner. However, the expression of TNFa was up-regulated in HeLa cells, but didn't change in A549 cells. While treating tumor cells with G-Rh2 respectively combined with ER antagonist MPP, PHTPP and ICI 182,780, compared to the control group, the expression of ERa, ERβ, TNFa were not affected by MPP,but affected by PHTPP and ICI182,780 larger. The expression of ERa and ERβin the G-Rh2 combined with PHTPP and ICI182,780 treatment group were lower, and the expression of TNFa in HeLa cells was reduced, but the expression of TNFa did not change in A549 cells.Conclusively, G-Rh2 can induce apoptosis of HeLa cells through the G1 cell cycle arrest and regulating the expression level of estrogen receptor ERα, ERβand TNFα.And it also can induce apoptosis of A549 cells through the G1 cell cycle arrest and regulating the expression level of ERa and ERβto inhibit the proliferation of tumor cells. ERαor/and ERβmay be as the common and critical signal protein of G-Rh2-induced-apoptosis in all the tumor cells.
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