• 華中科技大學(xué)協(xié)和深圳醫(yī)院（廣東深圳，518052）1 胃腸外科，2 中心實驗室，3 消化內(nèi)科;

【摘要】　目的　 探討凋亡抑制蛋白Livin與凋亡蛋白Caspase-3在結(jié)直腸腺瘤-癌序列中的表達變化及其相關(guān)性。　方法　 2006年7月—2009年12月，采用免疫組織化學(xué)染色鏈霉菌抗生物素蛋白-過氧化物酶鏈接法streptavidin-peroxidese，SP）法檢測18例正常黏膜、84例結(jié)直腸腺瘤、72例結(jié)直腸癌中Livin及Caspase-3的表達情況。　結(jié)果　 結(jié)直腸腺瘤組織中Livin蛋白的陽性表達率明顯高于正常黏膜組織（P lt;0.05），而低于腺癌組（P lt;0.05）；腺瘤組內(nèi)絨毛狀腺瘤與管狀腺瘤相比較，Livin蛋白表達率差異有統(tǒng)計學(xué)意義（P lt;0.05）。結(jié)直腸腺瘤組織中Caspase-3的陽性表達率明顯高于正常黏膜組織（P lt;0.05）；而腺瘤組織與癌組織之間Caspase-3陽性表達率差異（P lt;0.05）；腺瘤組內(nèi)絨毛狀腺瘤與管狀腺瘤相比較，Caspase-3蛋白陽性表達率差異無統(tǒng)計學(xué)意義（P gt;0.05）。Livin表達與Caspase-3表達呈負相關(guān)（P lt;0.05）。　結(jié)論　 凋亡抑制蛋白Livin參與了大腸腫瘤的發(fā)生，且在大腸腺瘤-腺癌階段起到了重要作用；凋亡抑制蛋白Livin與Caspase-3表達呈負相關(guān)，抑制Caspase-3蛋白的活性可能是Livin促進結(jié)腸癌發(fā)生的途徑之一。
【Abstract】　Objective　 To investigate the expression of Livin and Caspase-3 among colorectal adenoma-carcinoma sequence, and to identify the relationship between Livin and Caspase-3 expression in colorectal adenoma-carcinoma sequence.　Methods　 Formalin-fixed paraffin embedded colorectal tissues from 174 patients, including 84 adenomas, 72 carcinomas, and 18 normal mucosa, were examined for expression of Livin and Caspase-3 by streptavidin-peroxidase (SP) immunohistochemistry between July 2006 and December 2009.　Results　 The positive rates of Livin protein expression in colorectal adenoma was significantly higher than that in normal mucosa (P lt;0.05), but lower than that in adenocarcinoma (P lt;0.05); the expression of Livin in tubular adenoma was significantly higher than that in villous adenoma (P lt;0.05). The positive rates of Caspase-3 protein expression in colorectal adenoma were significantly higher than that in normal mucosa and carcinoma (P lt;0.05), and the difference in positive rate of Caspase-3 expression was not significant between the villous adenoma and tubular adenoma (P gt;0.05). Livin expression had negative correlation with the Caspase-3 expression (P gt;0.05).　Conclusion　 The difference in expression of Livin between adenoma and adenocarcinoma indicates the potential value of it in carcinogenesis of colorectal cancer, which suggestes that suppressing Caspase-3 protein activity is one of the channels by which livin promotes colorectal carcinogenesis.

引用本文： 王永,宋怡才,尹作文,喻軍,劉軍輝,李一帆,郭梅梅. Livin和Caspase-3在結(jié)直腸腺瘤-癌序列中的表達及相關(guān)性研究. 華西醫(yī)學(xué), 2011, 26(6): 878-881. doi: 復(fù)制

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10. 　Crnkovic-Mertens I, Hoppe-Seyler F, Butz K. Induction of apoptosis in tumor cells by siRNA-mediated silencing of the livin/ML-IAP/KIAP gene [J]. Oncogene, 2003, 22(51): 8330-8336.
11. 　Liu B, Han M, Wen JK, et al. Livin/ML-IAP as a new target for cancer treatment [J]. Cancer Letter, 2007, 250(2): 168-176.
12. 　Vucic D, Frankin MC, Walweber HJ, et al. Engineering ML-IA P to produce an extraordinarily potent Caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IA P [J]. Biochem J, 2005, 385(1): 11-20.
13. 　Nachmias B, Ashhab Y, Bucholtz V, et al. Caspase-mediated cleavage converts Livin from an antiapoptotic to a proapoptotic factor implication for drug-resistant melanoma [J]. Cancer Res, 2003, 63(10): 6340-6349.
14. 　石亮, 陳曉東, 林向陽. 細胞凋亡抑制蛋白研究進展 [J]. 國際檢驗醫(yī)學(xué)雜志, 2007, 28(2): 153-157.
  1. 1. 　Jemal A, Siegel R, Ward E, et al. Cancer statistics[J]. CA Cancer J Clin, 2007, 57(1): 43-66.
  2. 2. 　Tannapfel A, Neid M, Aust D, et al. The origins of colorectal carcinoma: specific nomenclature for different pathways and precursor lesions[J]. Dtsch Arztebl Int, 2010, 107(43): 760-766.
  3. 3. 　Hiroshi K, Masao T, Hisashi S, et al. Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis[J]. Cancer, 2001, 91(11): 2026-2032.
  4. 4. 　Huerta S, Goulet EJ, Livingston EH. Colon cancer and apoptosis[J]. Am J Surg, 2006, 191(4): 517-526.
  5. 5. 　Rupnarain C, Dlamini Z, Naicker S, et al. Colon cancer: genomics and apoptotic events[J]. Biol Chem, 2004, 385(6): 449-464.
  6. 6. 　Watson AJM. An overview of apoptosis and the prevention of colorectal cancer[J]. Crit Rev Oncolo/Hematolo, 2006, 57(2): 107-121.
  7. 7. 　Lin JH, Deng G, Huang Q, et al. KIAP, a novel member of the inhibitor of apoptosis protein family [J]. Biochem Biophys Res Commun, 2000, 279(3): 820-831.
  8. 8. 　Kasof GM, Gomes BC. Livin, a novel inhibitor of apoptosis protein family member [J]. J Biol Chem, 2001, 276(5): 3238-3246.
  9. 9. 　Vucic D, Stennicke HR, Pisabarro MT, et al. ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas [J]. Curr Biol, 2000, 10(21): 1359-1366.
  10. 10. 　Crnkovic-Mertens I, Hoppe-Seyler F, Butz K. Induction of apoptosis in tumor cells by siRNA-mediated silencing of the livin/ML-IAP/KIAP gene [J]. Oncogene, 2003, 22(51): 8330-8336.
  11. 11. 　Liu B, Han M, Wen JK, et al. Livin/ML-IAP as a new target for cancer treatment [J]. Cancer Letter, 2007, 250(2): 168-176.
  12. 12. 　Vucic D, Frankin MC, Walweber HJ, et al. Engineering ML-IA P to produce an extraordinarily potent Caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IA P [J]. Biochem J, 2005, 385(1): 11-20.
  13. 13. 　Nachmias B, Ashhab Y, Bucholtz V, et al. Caspase-mediated cleavage converts Livin from an antiapoptotic to a proapoptotic factor implication for drug-resistant melanoma [J]. Cancer Res, 2003, 63(10): 6340-6349.
  14. 14. 　石亮, 陳曉東, 林向陽. 細胞凋亡抑制蛋白研究進展 [J]. 國際檢驗醫(yī)學(xué)雜志, 2007, 28(2): 153-157.