COX-2抑制剂塞来昔布联合二甲双胍对DEN诱导SD大鼠肝癌预防作用研究
发布时间:2022-02-14 12:42
目的:COX-2抑制剂塞来昔布(Celecoxib)和二甲双胍是临床常用药物,近年来发现两种药物都具有抗肿瘤效应,但临床研究表明单独使用其中一种药物不能有效降低肝癌术后复发率。本研究旨在观察两种药物联合应用能否抑制DEN诱导的大鼠肝癌发生,同时检测p-mTOR、p-AMPK在大鼠及人肝癌组织中的表达,通过p-mTOR、p-AMPK在肝癌组织中的变化探讨二甲双胍联合塞来昔布在肝癌的可能的抗肿瘤机制。方法:1.体外培养人肝癌细胞株HepG2和HCCLM3,96孔板中每孔种20000个细胞,分3组:塞来昔布50mM;二甲双胍500 uM;塞来昔布50mM+二甲双胍0.5 mM,三组肝癌细胞加药处理48小时,利用MTT法检测各组药物对细胞活性的影响2.选用近交系的SD雄性大鼠98只,随机选择10只作为正常组,实验过程中不予特殊处理。余下88只随机分为4组,每组22只:二甲双胍组,塞来昔布组,联合用药组,对照组。每只大鼠均腹腔注射DEN(50mg/kg,1次/周),共18次。二甲双胍组按二甲双胍300mg/(kg.d)灌胃给药,塞来昔布组按塞来昔布100mg/(kg.d)灌胃给药,联合用药组按二...
【文章来源】:广西医科大学广西壮族自治区
【文章页数】:86 页
【学位级别】:硕士
【部分图文】:
推测的COX-2抑制剂(塞来昔布)联合二甲双胍靶向mTOR抑制肝癌干细胞生物学特性的分
诱导 SD 大鼠肝癌预防作用研究 2018 届硕士学位论文30图4-4 各组大鼠肝脏大体表现如图 4-4 所示:(1)DEN 组大鼠肝脏质地粗糙,色暗,表面凹凸不平,可见大小不等的灰白色癌结节,伴暗红色血肿;(2)塞来昔布组肝脏体积稍大,外形及边缘基本正常,可见约 2*1.5cm 的灰白色肿物;(3)二甲双胍组大鼠肝脏饱满,边缘变钝,表面可见白色颗粒状硬化小结节,无坏死及出血;(4)联合用药组大鼠肝脏外形及边缘基本正常,颜色暗红,肝脏表面可见少许淡黄色小结节,直径在 1-3mm 以内,数量明显少于其他用药组;(5)正常组大鼠肝脏组织呈深红色
324.4.2 大鼠肝脏组织 HE 染色图4-5 大鼠肝脏病理组织HE染色(×100)注:A 正常肝组织:可见正常肝小叶,肝细胞结构正常,胞核等大圆形,无其他细胞侵润B 肝硬化组织:可见大小不等的肝硬化假小叶形成,肝细胞胞核变形,可见肝细胞异型性增生C 肝癌及癌旁组织:可见排列呈粗大的梁索状或团状的癌细胞与癌旁正常组织,癌细胞胞核深染变形D 肝癌组织:癌细胞呈片状、弥漫性排列,细胞核和细胞质染色变深,微血管因严重受压而不明显。Figure 4-5 :HE staining (x 100) of liver pathological tissue in ratsNote: A normal liver tissue: normal hepatic lobules, normal hepatic cells, large round nuclei and no othercell invasion.B liver cirrhosis: the formation of pseudo lobules in different sizes of liver cirrhosis, thedeformation of the nuclei of hepatocytes, and the atypical hyperplasia of hepatic cells.C liver cancer and paracancerous tissue: visible cells with large girdled or lump like cancer cells andadjacent normal tissues, and nuclei of cancer cells are deeply stained.D liver cancer tissue: the cancer cells are plate-like and diffuse, the nuclei and cytoplasm are staineddeeper, and the microvessels are not obviously due to severe pressure.4.5、大鼠成瘤率我们于第 19 周采取腹腔注射麻醉药的方式处死所有大鼠,共计 77 只,
【参考文献】:
期刊论文
[1]MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis b- and c-related-hepatocellularcarcinoma[J]. Sirio Fiorino,Maria Letizia Bacchi-Reggiani,Michela Visani,Giorgia Acquaviva,Adele Fornelli,Michele Masetti,Andrea Tura,Fabio Grizzi,Matteo Zanello,Laura Mastrangelo,Raffaele Lombardi,Luca Di Tommaso,Arrigo Bondi,Sergio Sabbatani,Andrea Domanico,Carlo Fabbri,Paolo Leandri,Annalisa Pession,Elio Jovine,Dario de Biase. World Journal of Gastroenterology. 2016(15)
[2]索拉非尼联合塞来昔布在体外对肝癌HepG2细胞的影响[J]. 周善学,叶小磊,赵亚荣,应福明,冯雪峰,范天逸,李贤杰. 实用药物与临床. 2015(05)
[3]Metformin does not improve survival in patients with hepatocellular carcinoma[J]. Mamatha Bhat,Roongruedee Chaiteerakij,William S Harmsen,Cathy D Schleck,Ju Dong Yang,Nasra H Giama,Terry M Therneau,Gregory J Gores,Lewis R Roberts. World Journal of Gastroenterology. 2014(42)
[4]α-干扰素和环氧合酶-2抑制剂对人肝癌细胞生长的抑制作用[J]. 邱晓昕,刘景诗,左朝晖. 中华实验外科杂志. 2014 (09)
[5]Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease[J]. Valter Donadon,Massimiliano Balbi,Michela Ghersetti,Silvia Grazioli,Antonio Perciaccante,Giovanni Della Valentina,Rita Gardenal,Maria Dal Mas,Pietro Casarin,Giorgio Zanette,Cesare Miranda. World Journal of Gastroenterology. 2009(20)
[6]塞来昔布对人肝癌细胞株增殖及凋亡的影响[J]. 徐志远,戴朝六,王宁. 肿瘤学杂志. 2008(11)
硕士论文
[1]塞来昔布对二乙基亚硝胺诱导的SD大鼠肝癌预防作用研究[D]. 齐亚鹏.广西医科大学 2017
本文编号:3624577
【文章来源】:广西医科大学广西壮族自治区
【文章页数】:86 页
【学位级别】:硕士
【部分图文】:
推测的COX-2抑制剂(塞来昔布)联合二甲双胍靶向mTOR抑制肝癌干细胞生物学特性的分
诱导 SD 大鼠肝癌预防作用研究 2018 届硕士学位论文30图4-4 各组大鼠肝脏大体表现如图 4-4 所示:(1)DEN 组大鼠肝脏质地粗糙,色暗,表面凹凸不平,可见大小不等的灰白色癌结节,伴暗红色血肿;(2)塞来昔布组肝脏体积稍大,外形及边缘基本正常,可见约 2*1.5cm 的灰白色肿物;(3)二甲双胍组大鼠肝脏饱满,边缘变钝,表面可见白色颗粒状硬化小结节,无坏死及出血;(4)联合用药组大鼠肝脏外形及边缘基本正常,颜色暗红,肝脏表面可见少许淡黄色小结节,直径在 1-3mm 以内,数量明显少于其他用药组;(5)正常组大鼠肝脏组织呈深红色
324.4.2 大鼠肝脏组织 HE 染色图4-5 大鼠肝脏病理组织HE染色(×100)注:A 正常肝组织:可见正常肝小叶,肝细胞结构正常,胞核等大圆形,无其他细胞侵润B 肝硬化组织:可见大小不等的肝硬化假小叶形成,肝细胞胞核变形,可见肝细胞异型性增生C 肝癌及癌旁组织:可见排列呈粗大的梁索状或团状的癌细胞与癌旁正常组织,癌细胞胞核深染变形D 肝癌组织:癌细胞呈片状、弥漫性排列,细胞核和细胞质染色变深,微血管因严重受压而不明显。Figure 4-5 :HE staining (x 100) of liver pathological tissue in ratsNote: A normal liver tissue: normal hepatic lobules, normal hepatic cells, large round nuclei and no othercell invasion.B liver cirrhosis: the formation of pseudo lobules in different sizes of liver cirrhosis, thedeformation of the nuclei of hepatocytes, and the atypical hyperplasia of hepatic cells.C liver cancer and paracancerous tissue: visible cells with large girdled or lump like cancer cells andadjacent normal tissues, and nuclei of cancer cells are deeply stained.D liver cancer tissue: the cancer cells are plate-like and diffuse, the nuclei and cytoplasm are staineddeeper, and the microvessels are not obviously due to severe pressure.4.5、大鼠成瘤率我们于第 19 周采取腹腔注射麻醉药的方式处死所有大鼠,共计 77 只,
【参考文献】:
期刊论文
[1]MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis b- and c-related-hepatocellularcarcinoma[J]. Sirio Fiorino,Maria Letizia Bacchi-Reggiani,Michela Visani,Giorgia Acquaviva,Adele Fornelli,Michele Masetti,Andrea Tura,Fabio Grizzi,Matteo Zanello,Laura Mastrangelo,Raffaele Lombardi,Luca Di Tommaso,Arrigo Bondi,Sergio Sabbatani,Andrea Domanico,Carlo Fabbri,Paolo Leandri,Annalisa Pession,Elio Jovine,Dario de Biase. World Journal of Gastroenterology. 2016(15)
[2]索拉非尼联合塞来昔布在体外对肝癌HepG2细胞的影响[J]. 周善学,叶小磊,赵亚荣,应福明,冯雪峰,范天逸,李贤杰. 实用药物与临床. 2015(05)
[3]Metformin does not improve survival in patients with hepatocellular carcinoma[J]. Mamatha Bhat,Roongruedee Chaiteerakij,William S Harmsen,Cathy D Schleck,Ju Dong Yang,Nasra H Giama,Terry M Therneau,Gregory J Gores,Lewis R Roberts. World Journal of Gastroenterology. 2014(42)
[4]α-干扰素和环氧合酶-2抑制剂对人肝癌细胞生长的抑制作用[J]. 邱晓昕,刘景诗,左朝晖. 中华实验外科杂志. 2014 (09)
[5]Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease[J]. Valter Donadon,Massimiliano Balbi,Michela Ghersetti,Silvia Grazioli,Antonio Perciaccante,Giovanni Della Valentina,Rita Gardenal,Maria Dal Mas,Pietro Casarin,Giorgio Zanette,Cesare Miranda. World Journal of Gastroenterology. 2009(20)
[6]塞来昔布对人肝癌细胞株增殖及凋亡的影响[J]. 徐志远,戴朝六,王宁. 肿瘤学杂志. 2008(11)
硕士论文
[1]塞来昔布对二乙基亚硝胺诱导的SD大鼠肝癌预防作用研究[D]. 齐亚鹏.广西医科大学 2017
本文编号:3624577
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