沉默黏着斑激酶表达抑制大肠癌转移的体内研究

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (2047 KB) HTML (0 KB)
输出: BibTeX | EndNote (RIS)

摘要目的：通过裸鼠实验研究，证实沉默黏着斑激酶（FAK）的表达能有效抑制大肠癌的转移。方法：将24只裸鼠随机分成3组：实验组、阴性对照组、未处理组，分别注射FAK稳定沉默的结肠癌细胞、阴性对照组的结肠癌细胞、未特殊处理的结肠癌细胞，每组各8只裸鼠。在SPF条件动物实验室饲养6周后处死裸鼠，观察原位成瘤率、病死率、瘤体生长、肝肺转移情况，通过HE染色、免疫组织化学染色研究FAK微转移灶、蛋白表达情况。结果：各组成瘤率均为100%。与阴性对照组及未处理组相比，实验组转移率、病死率和FAK蛋白表达明显降低（P＜0.05），且转移灶恶变程度更低、形态更好，而阴性对照组与未处理组差异无统计学意义（P＞0.05）。结论：通过shRNA介导的FAK基因沉默对SW620原位移植后的裸鼠肝肺转移有明显抑制，FAK有望成为治疗大肠癌转移的新靶点。

	服务
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	洪卫文1
	苏国强2
	应红安3
	林峰1
	梁卫东1

关键词 ：黏着斑激酶, SW620, 大肠肿瘤, 裸鼠, 转移

Abstract：Objective: Focal adhesion kinase gene silencing by Short Hairpin RNA can effectively inhibit colorectal cancer’s metastasis were confirmed through injection of FAK-knockdown colorectal cancer cells into nude mice. Methods: Twenty-four nude mice were randomly divided into three groups which were experimental group which inject FAK-knockdown colon cancer cells, negative control group whick inject negative control colon cancer cells and untreated group which inject untreated colon cancer cells. Nude mice were sacrificed after 6 weeks and tumor formation rate, mortality, tumor growth, liver and lung’s metastasis, miscrometastasis were observed and FAK protein expression were determined with HE staining and immunohistochemical staining. Results: Tumor formation rate was 100% in each group. Distant metastases, mortality and FAK protein expression of experimental group was significantly lower than that of the other two groups (P<0.05), meanwhile, the malignant lesion extent was lighter. While negative control group and untreated group were not significantly different (P>0.05). Conclusion: Lentiviral packaging shRNA-mediated FAK gene silencing can significantly inhibit liver and lung metastasis of colorectal cancer. FAK is expected to be a new target for treatment of colon cancer metastasis.

Key words： focal adhesion kinase SW620 colorectal neoplasms nude mouse metastasis

收稿日期: 2014-02-18

作者简介: 洪卫文（1983-），男，福建龙岩人，住院医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2015/V45/I7/497

[1] Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in Europe in 2006[J]. Ann Oncol, 2007, 18(6): 581-592.
[2] Jemal A, Siegel R, Ward E, et al. Cancer statistics[J]. CA Cancer J Clin, 2009, 59(4): 225-249.
[3] Saletti P, Cavalli F. Metastatic colorectal cancer[J]. Cancer Treat Rev, 2006, 32(7): 557-571.
[4] Tol Jolien, Punt CJ. Monoclonal antibodies in the treatment of metastatic colorectal cancer: A review[J]. Clinical Therapeutics, 2010, 32(3): 437-453.
[5] 洪卫文, 苏国强, 应红安, 等. 稳定沉默黏着斑激酶结肠癌细胞株SW620的建立[J]. 温州医科大学学报, 2014, 44 (3): 201-204.
[6] 倪孔海, 翁志梁, 王思齐, 等. 粘着斑激酶在人良性前列腺增生组织中的表达及其意义[J]. 温州医学院学报, 2004, 34(4): 262-264.
[7] Seo CH, Jeong H, Feng Y, et al. Micropit surfaces designed for accelerating osteogenic differentiation of murine mesenchymal stem cells via enhancing focal adhesion and actin polymerization[J]. Biomaterials, 2013, 12(35): 2245-2252.
[8] 孙晓杰, 黄常志. PI3K-Akt信号通路与肿瘤[J]. 世界华人消化杂志, 2006, 14(3): 306-311.
[9] Yu HG, Tong SL, Ding YM, et al. Enhanced expression of cholecystokinin-2 receptor promotes the progression of colon cancer through activation of focal adhesion kinase[J]. Int J Cancer, 2006, 119(12): 2724-2732.
[10] Stoeck A, Gast D, Sanderson MP, et al. L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in ovarian carcinoma cells[J]. Gynecol Oncol, 2007, 104(2): 461-469.
[11] Serrels A, Canel M, Brunton VG, et al. Src/FAK-mediated regulation of E-cadherin as a mechanism for controlling collective cell movement: insights from in vivo imaging[J].Cell Adh Migr, 2011, 5: 360-365.
[12] 袁周, 郑起, 黄新余, 等. 抑制黏着斑激酶表达对人肝癌细胞转移潜能的作用[J]. 中华外科杂志, 2007, 45(19): 1350-1353.
[13] Figel S, Gelman I. Focal adhesion kinase controls prostate cancer progression via intrinsic kinase and scaffolding functions[J]. Anticancer Agents Med Chem, 2011, 11(7): 607-616.
[14] Simmonds PC, Primrose JN, Colquitt JL, et al. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies[J]. Br J Surg, 2006, 94 (7): 982-999.
[15] Iwasaki A, Shirakusa T, Yamashita Y, et al. Characteristic differences between patients who have undergone surgical treatment for lung metastasis or hepatic metastasis from colorectal cancer[J]. Thorac Cardiov Surg, 2005, 53(6): 358-364.