目的 通過(guò)在肝特異性胰島素樣生長(zhǎng)因子-1(insulin-like growth factor 1,IGF-1)基因缺失(LID)小鼠體內(nèi)建立穩(wěn)定的原發(fā)性結(jié)直腸癌模型,探討IGF-1 與小鼠原發(fā)性結(jié)直腸癌發(fā)生可能存在的關(guān)系。
方法 ①建立結(jié)直腸癌模型: 使用LID小鼠(實(shí)驗(yàn)組)和BALB/c小鼠(對(duì)照組)。LID小鼠體循環(huán)中的IGF-1水平僅為BALB/c小鼠的25%,用化學(xué)致癌劑1,1二甲基肼(DMH)頸部皮下注射誘導(dǎo)原發(fā)性結(jié)直腸腫瘤。②應(yīng)用免疫組織化學(xué)法(SP)對(duì)80只模型小鼠的結(jié)直腸癌組織及其癌旁組織標(biāo)本進(jìn)行IGF-1的抗原染色,將染色結(jié)果與小鼠的體質(zhì)量及結(jié)直腸的致癌情況進(jìn)行綜合分析。
結(jié)果 ?、賹?shí)驗(yàn)組和對(duì)照組小鼠的體質(zhì)量在注藥后與注藥前比較體質(zhì)量均減輕,注藥后18及24周時(shí)與各組注藥前相應(yīng)時(shí)相比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。②IGF-1免疫組化染色結(jié)果: IGF-1在結(jié)直腸癌中的表達(dá)部位是在癌細(xì)胞的核周胞漿中,呈彌散狀分布。③IGF-1在實(shí)驗(yàn)組和對(duì)照組結(jié)直腸癌組織及癌旁組織中表達(dá)陽(yáng)性者分別為6/7只、2/7只及13/16只、7/16只。2組結(jié)直腸癌組織中的IGF-1表達(dá)陽(yáng)性者均高于癌旁組織(P<0.05)。實(shí)驗(yàn)組和對(duì)照組兩組間癌組織和癌旁組織中的IGF-1的表達(dá)陽(yáng)性情況差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。
結(jié)論 在致癌劑DMH誘導(dǎo)的結(jié)直腸癌模型中,IGF-1 對(duì)結(jié)直腸癌的發(fā)生和發(fā)展起重要作用。
引用本文: 黃桂林,吳毅平,雷娜. 胰島素樣生長(zhǎng)因子-1在原發(fā)性結(jié)直腸癌中表達(dá)的研究. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 16(9): 693-697. doi: 復(fù)制
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- 1. Ma J, Pollak MN, Giovannucci E, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-Ⅰ and IGF-binding protein-3 [J]. J Natl Cancer Inst, 1999; 91(7): 620-625.
- 2. 張珊, 陳國(guó)慶, 唐鴻波, 等. 血清胰島素樣生長(zhǎng)因子-1對(duì)癌性惡病質(zhì)小鼠營(yíng)養(yǎng)狀況的影響 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008; 15(2): 112-115.
- 3. Wolpin BM, Michaud DS, Giovannucci EL, et al. Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer [J]. Cancer Res, 2007; 67(16): 7923-7928.
- 4. 任玉萍, 葉子榮, 唐泓波, 等. 利用IGF-1基因敲除鼠乳腺癌模型研究IGF-1對(duì)血管生成的影響 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008; 15(11): 820-824.
- 5. Sridhar SS, Goodwin PJ. Insulin-insulin-like growth factor axis and colon cancer [J]. J Clin Oncol, 2009; 27(2): 165-167.
- 6. 牛堅(jiān), 李向農(nóng), 韓澤廣. 運(yùn)用siRNA建立穩(wěn)定低表達(dá)IGF1R基因的肝癌細(xì)胞株的實(shí)驗(yàn)研究 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2007; 14(6): 679-684.
- 7. Hankinson SE, Willett WC, Colditz GA, et al. Circulating concentrations of insulin-like growth factor-Ⅰ and risk of breast cancer [J]. Lancet, 1998; 351(9113): 1393-1396.
- 8. Chan JM, Stampfer MJ, Giovannucci E, et al. Plasma insulin-like growth factor-Ⅰ and prostate cancer risk: a prospective study [J]. Science, 1998; 279(5350): 563-566.
- 9. Yu H, Spitz MR, Mistry J, et al. Plasma levels of insulin-like growth factor-Ⅰ and lung cancer risk: a case-control analysis [J]. J Natl Cancer Inst, 1999; 91(2): 151-156.
- 10. Yakar S, Liu JL, Stannard B, et al. Normal growth and development in the absence of hepatic insulin-like growth factor Ⅰ [J]. Proc Natl Acad Sci USA, 1999; 96(13): 7324-7329.
- 11. 李玉林主編. 病理學(xué) [M]. 第6版. 北京: 人民衛(wèi)生出版社, 2004: 95-111.
- 12. 郭寶文, 吳敏蘭. IGF-Ⅱ、IGF-ⅠR 在大腸癌中的表達(dá) [J]. 山東醫(yī)藥, 2005; 45(10): 6-8.
- 13. Takahari D, Yamada Y, Okita NT, et al. Relationships of insulin-like growth factor-1 receptor and epidermal growth factor receptor expression to clinical outcomes in patients with colorectal cancer [J]. Oncology, 2009; 76(1): 42-48.
- 14. Wu Y, Yakar S, Zhao L, et al. Circulating insulin-like gro-wth factor-Ⅰ levels regulate colon cancer growth and metastasis [J]. Cancer Res, 2002; 62(4): 1030-1035.
- 15. 楊琳, 郭寶文, 趙魁. IGF-Ⅰ、IGF-Ⅱ 在大腸癌中的表達(dá)及臨床意義 [J]. 山東醫(yī)藥, 2005; 45(9): 35-36.
- 16. 吳毅平, Cui C, Miyoshi K, 等. 肝特異性胰島素樣生長(zhǎng)因子Ⅰ基因缺失鼠原發(fā)性乳腺癌模型的建立 [J]. 華中科技大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2004; 33(2): 180-183.
- 17. Durai R, Yang W, Gupta S, et al. The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge [J]. Int J Colorectal Dis, 2005; 20(3): 203-220.
- 18. Hakam A, Yeatman TJ, Lu L, et al. Expression of insulin-like growth factor-1 receptor in human colorectal cancer [J]. Hum Pathol, 1999; 30(10): 1128-1133.
- 19. DeLellis K, Rinaldi S, Kaaks RJ, et al. Dietary and lifestyle correlates of plasma insulin-like growth factor-Ⅰ (IGF-Ⅰ) and IGF binding protein-3 (IGFBP-3): the multiethnic cohort [J]. Cancer Epidemiol Biomarkers Prev, 2004; 13(9): 1444-1451.
- 20. Jenkins PJ, Bustin SA. Evidence for a link between IGF-Ⅰ and cancer [J]. Eur J Endocrinol, 2004; 151 Suppl 1: S17-S22.