組蛋白去乙酰化酶抑制劑丙戊酸通過PI3K/AKT/mTOR信號通路抑制胃癌發(fā)生發(fā)展的作用研究
發(fā)布時間:2021-11-27 04:13
研究背景:胃癌高居全球癌癥發(fā)病率的第四位、死亡率第三位。據(jù)統(tǒng)計,全球每年約新增胃癌病例一百萬人次,且將近88%的病例出現(xiàn)在發(fā)展中國家,尤其是中國等處于東亞的發(fā)展中國家。手術(shù)切除仍然是臨床上治療胃癌的首選方法,但對于中晚期患者該方法卻不能有效改善患者預(yù)后。分子靶向治療是近幾年發(fā)展迅速的一種新型胃癌治療方式。目前,雖然臨床上應(yīng)用的胃癌靶向藥物有很多,例如以HER2、VEGF、EGFR和mTOR等為靶標(biāo)藥物,但均存在靶向效率低、個體耐藥性高等缺點。因此,尋找一種新型的分子靶向藥物來改善胃癌患者的治療刻不容緩。丙戊酸(VPA)是一種臨床上用于治療癲癇和雙向情感障礙的神經(jīng)類藥物。同時,它也是一種特異性的組蛋白脫乙酰酶(HDAC)抑制劑,可以抑制腫瘤細胞的增殖、誘導(dǎo)凋亡的發(fā)生。大量的研究顯示,VPA在抑制血液系統(tǒng)腫瘤和神經(jīng)系統(tǒng)腫瘤方面具有較好的藥效,但在治療胃癌方面則尚無報道。研究目的:通過體外實驗探討VPA對于胃癌細胞生物學(xué)功能的影響,并闡明其可能的分子機制。材料和方法:應(yīng)用噻唑藍實驗(MTT)檢測VPA對于不同分化程度的4種胃癌細胞株AGS、MKN-28、MKN-74和SGC-7901活性的抑...
【文章來源】:延邊大學(xué)吉林省 211工程院校
【文章頁數(shù)】:68 頁
【學(xué)位級別】:碩士
【文章目錄】:
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
攻讀碩士學(xué)位期間取得的科研業(yè)績
致謝
【參考文獻】:
期刊論文
[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]丙戊酸誘導(dǎo)白血病細胞凋亡機理的實驗研究[J]. 薛紅漫,李文益,郭海霞,夏焱,陳琴,劉勇. 中華兒科雜志. 2005(12)
[6]Mechanism and its regulation of tumor-induced angiogenesis[J]. Manoj Kumar Gupta. World Journal of Gastroenterology. 2003(06)
本文編號:3521540
【文章來源】:延邊大學(xué)吉林省 211工程院校
【文章頁數(shù)】:68 頁
【學(xué)位級別】:碩士
【文章目錄】:
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
攻讀碩士學(xué)位期間取得的科研業(yè)績
致謝
【參考文獻】:
期刊論文
[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]丙戊酸誘導(dǎo)白血病細胞凋亡機理的實驗研究[J]. 薛紅漫,李文益,郭海霞,夏焱,陳琴,劉勇. 中華兒科雜志. 2005(12)
[6]Mechanism and its regulation of tumor-induced angiogenesis[J]. Manoj Kumar Gupta. World Journal of Gastroenterology. 2003(06)
本文編號:3521540
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