• 1.華中科技大學(xué)同濟醫(yī)學(xué)院同濟醫(yī)院整形外科(武漢 430030);;
  • 2.石河子大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院普外二科(新疆石河子 832002);

目的 　通過在肝特異性胰島素樣生長因子-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(實驗組)和BALB/c小鼠(對照組)。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80只模型小鼠的結(jié)直腸癌組織及其癌旁組織標本進行IGF-1的抗原染色，將染色結(jié)果與小鼠的體質(zhì)量及結(jié)直腸的致癌情況進行綜合分析。
結(jié)果 　①實驗組和對照組小鼠的體質(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周時與各組注藥前相應(yīng)時相比較差異有統(tǒng)計學(xué)意義(P＜0.05)。②IGF-1免疫組化染色結(jié)果: IGF-1在結(jié)直腸癌中的表達部位是在癌細胞的核周胞漿中，呈彌散狀分布。③IGF-1在實驗組和對照組結(jié)直腸癌組織及癌旁組織中表達陽性者分別為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表達陽性者均高于癌旁組織(P＜0.05)。實驗組和對照組兩組間癌組織和癌旁組織中的IGF-1的表達陽性情況差異均無統(tǒng)計學(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. 胰島素樣生長因子-1在原發(fā)性結(jié)直腸癌中表達的研究. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(9): 693-697. doi: 復(fù)制

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, 陳國慶, 唐鴻波, 等. 血清胰島素樣生長因子-1對癌性惡病質(zhì)小鼠營養(yǎng)狀況的影響 [Ｊ]. 中國普外基礎(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對血管生成的影響 [Ｊ]. 中國普外基礎(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, 李向農(nóng), 韓澤廣. 運用siRNA建立穩(wěn)定低表達IGF1R基因的肝癌細胞株的實驗研究 [Ｊ]. 中國普外基礎(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 [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(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.
  1. 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. 2. 張珊, 陳國慶, 唐鴻波, 等. 血清胰島素樣生長因子-1對癌性惡病質(zhì)小鼠營養(yǎng)狀況的影響 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(2): 112-115.
  3. 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. 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對血管生成的影響 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(11): 820-824.
  5. 5. Sridhar SS, Goodwin PJ. Insulin-insulin-like growth factor axis and colon cancer [Ｊ]. J Clin Oncol, 2009; 27(2): 165-167.
  6. 6. 牛堅, 李向農(nóng), 韓澤廣. 運用siRNA建立穩(wěn)定低表達IGF1R基因的肝癌細胞株的實驗研究 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志, 2007; 14(6): 679-684.
  7. 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. 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. 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. 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. 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. 12. 郭寶文， 吳敏蘭. IGF-Ⅱ、IGF-ⅠR 在大腸癌中的表達 [Ｊ]. 山東醫(yī)藥, 2005; 45(10): 6-8.
  13. 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. 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. 15. 楊琳， 郭寶文， 趙魁. IGF-Ⅰ、IGF-Ⅱ 在大腸癌中的表達及臨床意義 [Ｊ]. 山東醫(yī)藥, 2005; 45(9): 35-36.
  16. 16. 吳毅平, Cui C, Miyoshi K, 等. 肝特異性胰島素樣生長因子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(醫(yī)學(xué)版), 2004; 33(2): 180-183.
  17. 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. 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. 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. 20. Jenkins PJ, Bustin SA. Evidence for a link between IGF-Ⅰ and cancer [Ｊ]. Eur J Endocrinol, 2004; 151 Suppl 1: S17-S22.