p53和Ras信号相互作用调节卵巢癌上皮细胞间质转化（EMT）、衰老和凋亡的机制研究

发布时间：2018-04-22 17:57

本文选题：卵巢癌 + p53抑癌基因　；参考：《复旦大学》2014年硕士论文

【摘要】：目的：探索p53和Ras信号相互作用调节卵巢癌上皮细胞间质转化(EMT)、细胞衰老和细胞凋亡的机制。方法：在人卵巢浆液性乳头状囊腺癌细胞系SKOV3中导入能够诱导表达的野生型p53以及H-Ras的四种不同突变体,建立细胞模型。在此基础上,围绕细胞衰老、细胞凋亡及EMT等,在细胞水平和动物水平上对p53和Ras在卵巢癌形成与发生过程中的相互作用进行了研究。结果：H-Ras(V12)能够促进细胞凋亡和衰老的发生；H-Ras(E38)能够较明显促进凋亡的发生；H-Ras(S35)、H-Ras(C40)对细胞凋亡和衰老的诱导不明显。诱导p53表达后,p53能够促进各组肿瘤细胞凋亡和衰老,同时H-ras突变体蛋白的表达能够对抗p53的抑癌作用。H-Ras (V12)、H-Ras (C40)具有较强的诱导EMT发生的能力。p53表达后,导入H-Ras (V12)、H-Ras (S35)、H-Ras (E38)的细胞的迁移能力和EMT的发生受到抑制；但对导入H-Ras(C40)突变体的细胞抑制作用不明显。H-Ras (V12)、H-Ras (E38)导入细胞后体外克隆形成能力及体内成瘤能力都减弱；H-Ras(S35)体外克隆形成能力及体内成瘤能力影响不明显,p53表达能够在体内和体外抑制其克隆形成及生长；H-Ras(C40)导入细胞后,细胞体外克隆形成能力增强,生长速度加快,在实验动物体内H-Ras(C40)能够促进肿瘤的生长,且不能被p53抑制。结论：不同的H-ras突变体在卵巢癌的形成与发展过程中有不同的作用；p53的表达并不能完全抑制突变H-Ras在卵巢癌中的作用。目的探讨树舌灵芝提取物在实验动物体内对三阴乳腺癌的抑制作用。方法建立三阴乳腺癌荷瘤小鼠模型,观察树舌灵芝提取物对三阴乳腺癌的抑制作用作用;通过免疫组织化学染色,研究树舌灵芝提取物抗肿瘤作用的机理。结果实体瘤模型中,树舌灵芝组移植瘤重量和体积明显低于对照组(P0.05),微血管密度值也低于对照组(P0.05);免疫组织化学染色结果显示：树舌灵芝组TSP-1表达升高;Cyclin D1表达降低。结论树舌灵芝提取物在实验动物体内,能通过抑制肿瘤组织中血管的生成并通过调节细胞周期来抑制肿瘤细胞的过度增殖,从而实现对三阴乳腺癌的抑制作用。
[Abstract]:Aim: to explore the mechanism of p53 and Ras signal interaction in regulating epithelial epithelial stromal transformation (EMT), cell senescence and apoptosis. Methods: four different mutants of wild-type p53 and H-Ras were introduced into human ovarian serous papillary cystadenocarcinoma cell line SKOV3. On this basis, the interaction of p53 and Ras in the formation and development of ovarian cancer was studied at cell level and animal level, focusing on cell senescence, apoptosis and EMT. Results: the cell apoptosis and senescence were promoted by the cell apoptosis induced by the cell apoptosis induced by H RasN S35 and H RasN C40 (P < 0 05), and the induction of cell apoptosis and senescence was not obvious (P < 0 05), and the induction of cell apoptosis and senescence was not obvious (P < 0 05). After p53 expression was induced, p53 could promote apoptosis and senescence of tumor cells in each group. Meanwhile, the expression of H-ras mutant protein could antagonize the tumor suppressor effect of p53. H-Ras V12H-Ras C40) had a strong ability to induce the expression of EMT. The ability of migration and the occurrence of EMT were inhibited in the cells transfected with H-Ras V12, H-Ras S35 and H-Ras (E38). But the cell inhibitory effect on the transfected H-Ras-C40) mutant was not obvious. H-Ras V12HRAS-E38) after the introduction of the cell line, the ability of colony formation in vitro and the ability of tumorigenesis in vivo were both weakened, and the ability of clone formation in vitro and tumorigenic ability in vivo were not significantly affected by the expression of p53. In vivo and in vitro, inhibition of the formation and growth of H- Rasn C40 was induced into the cells. The ability of cell clone formation was enhanced and the growth rate was accelerated in vitro. H-RasC40) could promote the growth of tumor and could not be inhibited by p53. Conclusion: different H-ras mutants play different roles in the formation and development of ovarian cancer. The expression of p53 can not completely inhibit the role of mutant H-Ras in ovarian cancer. Objective to investigate the inhibitory effect of Ganoderma lucidum extract on triple-negative breast cancer in experimental animals. Methods the tumor bearing mice model of Sanyin breast cancer was established to observe the inhibitory effect of Ganoderma lucidum extract on Sanyin breast cancer, and to study the anti-tumor mechanism of Ganoderma lucidum extract by immunohistochemical staining. Results in the solid tumor model, the weight and volume of transplanted tumor in Ganoderma lucidum group was significantly lower than that in control group (P 0.05), and the microvessel density was lower than that in control group (P 0.05). The results of immunohistochemical staining showed that the expression of Cyclin D1 in Ganoderma lucidum group was increased and Cyclin D1 expression was lower than that in Ganoderma lucidum group. Conclusion the Ganoderma lucidum extract can inhibit the proliferation of tumor cells by inhibiting the angiogenesis in tumor tissues and regulating the cell cycle so as to achieve the inhibitory effect on triple-negative breast cancer.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.31

【共引文献】