组蛋白去乙酰化酶抑制剂丙戊酸通过PI3K/AKT/mTOR信号通路抑制胃癌发生发展的作用研究

发布时间：2021-11-27 04:13

　　研究背景:胃癌高居全球癌症发病率的第四位、死亡率第三位。据统计,全球每年约新增胃癌病例一百万人次,且将近88%的病例出现在发展中国家,尤其是中国等处于东亚的发展中国家。手术切除仍然是临床上治疗胃癌的首选方法,但对于中晚期患者该方法却不能有效改善患者预后。分子靶向治疗是近几年发展迅速的一种新型胃癌治疗方式。目前,虽然临床上应用的胃癌靶向药物有很多,例如以HER2、VEGF、EGFR和mTOR等为靶标药物,但均存在靶向效率低、个体耐药性高等缺点。因此,寻找一种新型的分子靶向药物来改善胃癌患者的治疗刻不容缓。丙戊酸（VPA）是一种临床上用于治疗癫痫和双向情感障碍的神经类药物。同时,它也是一种特异性的组蛋白脱乙酰酶（HDAC）抑制剂,可以抑制肿瘤细胞的增殖、诱导凋亡的发生。大量的研究显示,VPA在抑制血液系统肿瘤和神经系统肿瘤方面具有较好的药效,但在治疗胃癌方面则尚无报道。研究目的:通过体外实验探讨VPA对于胃癌细胞生物学功能的影响,并阐明其可能的分子机制。材料和方法:应用噻唑蓝实验（MTT）检测VPA对于不同分化程度的4种胃癌细胞株AGS、MKN-28、MKN-74和SGC-7901活性的抑... 

【文章来源】：延边大学吉林省 211工程院校

【文章页数】：68 页

【学位级别】：硕士

【文章目录】：
中文摘要
ABSTRACT
ABBREVIATIONS
1. INTRODUCTION
2. MATERIALS AND METHODS
    2.1 Materials
        2.1.1 Experimental reagents and instruments
    2.2 Methods
        2.2.1 Cell culture
        2.2.2 Cell viability assay
        2.2.3 Colony formation assay
        2.2.4 Flow cytometry
        2.2.5 Hoechest staining
        2.2.6 Immunofluorescence
        2.2.7 Protein extraction and western blot
        2.2.8 Acridine orange (AO) staining
        2.2.9 Electron microscopy
        2.2.10 Statistical analysis
3. RESULTS
    3.1 VPA suppressed gastric cancer cell proliferation and HDAC1/HDAC2 expressions in vitro
    3.2 VPA induced apoptosis in AGS and SGC-7901 gastric cancer cells
    3.3 VPA induces autophagy of gastric cancer cells
    3.4 VPA contributes to its cytotoxicity against gastric cancer cells via activation of the PI3K/Akt/mTORsignaling pathway
4. DISCUSSION
5. CONCLUSIONS
REFERENCES
攻读硕士学位期间取得的科研业绩
致谢


【参考文献】：
期刊论文
[1]Recent advances in the HER2 targeted therapy of gastric cancer[J]. Tasuku Matsuoka,Masakazu Yashiro.  World Journal of Clinical Cases. 2015(01)
[2]Medical management of gastric cancer:A 2014 update[J]. Elena Elimova,Hironori Shiozaki,Roopma Wadhwa,Kazuki Sudo,Qiongrong Chen,Jeannelyn S Estrella,Mariela A Blum,Brian Badgwell,Prajnan Das,Shumei Song,Jaffer A Ajani.  World Journal of Gastroenterology. 2014(38)
[3]Multimodal treatment of gastric cancer[J]. Ilaria Proserpio,Stefano Rausei,Sabrina Barzaghi,Francesco Frattini,Federica Galli,Domenico Iovino,Francesca Rovera,Luigi Boni,Gianlorenzo Dionigi,Graziella Pinotti.  World Journal of Gastrointestinal Surgery. 2014(04)
[4]Serum VEGFR-3 and survival of advanced gastric cancer patients treated with FOLFOX[J]. Xue-Feng Ni,Chang-Ping Wu,Jing-Ting Jiang,Department of Oncology,The Third Affiliated Hospital,Soochow University,Changzhou 213003,Jiangsu Province,China.  World Journal of Gastroenterology. 2010(17)
[5]丙戊酸诱导白血病细胞凋亡机理的实验研究[J]. 薛红漫,李文益,郭海霞,夏焱,陈琴,刘勇.  中华儿科杂志. 2005(12)
[6]Mechanism and its regulation of tumor-induced angiogenesis[J]. Manoj Kumar Gupta.  World Journal of Gastroenterology. 2003(06)



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