A Study Of Interaction Between P53 And Ras Signaling Regulating The EMT, Cell Senescence And Apoptosis In Ovarian Cancer

Objective:To explore detailed mechanism of the interaction between p53 and Ras signaling in regulation of epithelial-mesenchymal transition, cell senescence and apoptosis in ovarian cance。 Methods:We transfect ovarian cancer cell line SKOV3 with a inducible p53 expression system and different mutations of H-Ras gene. Then we used this model system to investigate the respective contributions of p53 and mutent H-Ras gene in cell senescence, apoptosis, EMT and the colony formation and tumorgenesis in vitro and in vivo. Results:the mutant H-Ras (V12) gene can promote apoptosis and cell senescence; H-Ras (E38) can obviously promote apoptosis; H-Ras (S35), H-Ras (C40) can not promote apoptosis and cell senescence obviously. The expression of p53 can promote apoptosis and cell senescence in each group, while the expression of H-ras mutations protein is able to resist the role of p53 as a tumor suppressor gene. H-Ras (V12) and H-Ras (C40) has a strong ability to induce EMT. The EMT and the migration of the cells which transformed by H-Ras (V12), H-Ras (S35), H-Ras (E38) was inhibited by p53. H-Ras (V12), H-Ras (E38) inhibit the colony formation and tumorgenesis when H-Ras (C40) promote cell growth, colony formation in vitro and the tumorgenesis in vivo. H-Ras (C40) can promote tumor growth, and can not be inhibited p53. The expression of p53 can inhibit the colony formation and tumorgenesis of all the cells except H-Ras (C40) transformed one. Conclusion:Different mutant H-ras gene mutant has a different role in tumorgenesis and development of ovarian cancer; expression of p53 could not completely inhibit the role of H-Ras mutations in ovarian cancer.Objective To study the inhibitory effect and mechanism of Ganoderma lipsiense on the growth of human triple-negative breast cancer cell line MDA-MB-231-HM in a mouse modle. Methods The mouse model of human triple-negative breast cancer was established by subcutaneous injection of 1.5x106 of MDA-MB-231-HM cells into BALB/c-nu mouse. The mouse model was used to test the effects of Ganoderma lipsiense on tumor growth and the mechanism of these effects were investigated in transplanted tumor by immunohistochemical technique. Results The average weight and volume of transplanted tumor of MDA-MB-231-HM cells in Ganoderma lipsiense group were lower than those in control group(P<0.05). The MVD of transplanted tumor in Ganoderma lipsiense group was also lower than that in control group(P<0.05). The expression of TSP-1 in tumor tissue was higher than that in control group, while the expression of in Ganoderma lipsiense group was lower than that in control group. Conclusion Ganoderma lipsiense shows obviously inhibitory effect on the growth of human triple-negative breast cancer cell line MDA-MB-231-HM in a mouse modle. The inhibitory mechanism maybe related to anti-angiogenic and cell cycle regulation effects of Ganoderma lipsiense on malignant proliferation and tumorigenicity of human triple-negative breast cancer cell line MDA-MB-231-HM; the up-regulation of TSP-1 and down-regulation of Cyclin Dl protein may involve in these effects.