• 南華大學(xué)附屬南華醫(yī)院普外科（湖南衡陽421001）;

目的總結(jié)Survivin基因在腫瘤中的作用。方法通過復(fù)習(xí)國內(nèi)、外文獻，回顧分析survivin的生物學(xué)特性及其在腫瘤基因治療與臨床應(yīng)用中的研究現(xiàn)狀。結(jié)果survivin基因是迄今為止發(fā)現(xiàn)的最強的凋亡抑制基因，主要是通過直接抑制caspase級聯(lián)反應(yīng)下游的終末子caspase-3和caspase-7的活性，從而發(fā)揮抗凋亡作用; survivin基因可通過加快腫瘤細胞由G1→S期的轉(zhuǎn)換以及使腫瘤細胞在G2/M期逃避對凋亡的識別而促進腫瘤細胞增殖、分化; survivin基因能通過血管形成因子（VEGF、bFGF、Ang-1和COX-2）在血管形成的中間環(huán)節(jié)發(fā)揮重要作用。結(jié)論Survivin可抑制腫瘤細胞的凋亡、促進腫瘤細胞增殖分化和腫瘤血管生成，提示其可能作為一種新的腫瘤標志物，成為檢測惡性腫瘤的指標。

引用本文： 周明利,張樹友. survivin基因在腫瘤中的作用研究進展. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(7): 779-782. doi: 復(fù)制

1. Andersen MH, Svane IM, Becker JC, et al. The universal character of the tumorassociated antigen survivin [J]. Clin Cancer Res, 2007, 13(20): 59915994.
2. Montorsi M, Maggioni M, Falleni M, et al. Survivin gene expression in chronic liver disease and hepatocellular carcinoma[J]. Hepatogastroenterology, 2007, 54(79): 20402044.
3. Kitamura H, Torigoe T, Honma I, et al. Expression and antigenicity of survivin, an inhibitor of apoptosis family member, in bladder cancer: implications for specific immunotherapy[J]. Urology, 2006, 67(5): 955959.
4. Ambrosini G, Adida C, Altieri DC. A novel antiapoptosis gene, survivin, expressed in cancer and lymphoma[J]. Nat Med, 1997, 3(8): 917921.
5. NikolovskaColeska Z, Meagher JL, Jiang S, et al. Interaction of a cyclic, bivalent smac mimetic with the xlinked inhibitor of apoptosis protein[J]. Biochemistry, 2008, 47(37): 98119824.
6. Colnaghi R, Connell CM, Barrett RM, et al. Separating the antiapoptotic and mitotic roles of survivin[J]. J Biol Chem, 2006, 281(44): 3345033456.
7. Knauer SK, Bier C, Schlag P, et al. The survivin isoform survivin3B is cytoprotective and can function as a chromosomal passenger complex protein[J]. Cell Cycle, 2007, 6(12): 15021509.
8. Atlasi Y, Mowla SJ, Ziaee SA. Differential expression of survivin and its splice variants, survivinDeltaEx3 and survivin2B, in bladder cancer[J]. Cancer Detect Prev, 2009, 32(4): 308313.
9. Suzuki A, Ito T, Kawano H, et al. Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fasmediated cell death[J]. Oncogene, 2000, 19(10): 13461353.
10. Verdecia MA, Huang H, Dutil E, et al. Structure of the human antiapoptotic protein survivin reveals a dimeric arrangement[J]. Nat Struct Biol, 2006, 7(7): 602608.
11. Marusawa H, Matsuzawa S, Welsh K, et al. HBXIP functions as a cofactor of survivin in apoptosis suppression[J]. EMBO J, 2003, 22(11): 27292740.
12. Zhao J, Tenev T, Martins LM, et al. The ubiquitinproteasome pathway regulates survivin degradation in a cell cycledependent manner[J]. J Cell Sci, 2000, 113 (Pt 23): 43634371.
13. Wolanin K, Piwocka K. Role of survivin in mitosis[J]. Postepy Biochem, 2007, 53(1): 1018.
14. Suzuki A, Hayashida M, Ito T, et al. Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16（INK4a）and Cdk2/cyclin E complex activation[J]. Oncogene, 2000, 19(29): 32253234.
15. Mita AC, Mita MM, Nawrocki ST, et al. Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics[J]. Clin Cancer Res, 2008, 14(16): 50005005.
16. Li YH, Hu CF, Shao Q, et al. Elevated expressions of survivin and VEGF protein are strong independent predictors of survival in advanced nasopharyngeal carcinoma[J]. J Transl Med, 2008, 6: 1.
17. Ma ACh, Lin R, Chan PK, et al. The role of survivin in angiogenesis during Zebrafish embryonic development[J]. BMC Dev Biol, 2007, 7: 50.
18. 孔令建, 趙晶, 曲波, 等. Survivin、COX2及VEGF在大腸癌中的表達及與腫瘤微血管密度的關(guān)系 [J]. 世界華人消化雜志, 2009, 17(20): 20482053.
19. Abe S, Hasegawa M, Yamamoto K, et al. Rapid induction of IAP family proteins and Smac/DIABLO expression after proapoptotic stimulation with doxorubicin in RPMI 8226 multiple myeloma cells[J]. Exp Mol Pathol, 2007, 83(3): 405412.
20. 管小青, 吳驥, 顧書成, 等. survivin與p53、Ki67在復(fù)發(fā)轉(zhuǎn)移性乳腺癌組織中表達及相關(guān)性研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(3): 290294.
21. 崔斐, 陳斌, 陳錦章, 等. 凋亡抑制蛋白Survivin和血管內(nèi)皮生長因子在肝細胞癌中的表達及其臨床意義 [J]. 南方醫(yī)科大學(xué)學(xué)報, 2008, 28(5): 761763.
22. Chao JI, Kuo PC, Hsu TS. Downregulation of survivin in nitric oxideinduced cell growth inhibition and apoptosis of the human lung carcinoma cells[J]. J Biol Chem, 2004, 279(19): 2026720276.
23. Li F, Ling X. Survivin study: an update of “what is the next wave”?[J]. J Cell Physiol, 2006, 208(3): 476486.
24. Romagnoli M, Séveno C, Bataille R, et al. Survivin in cancerology: molecular aspects and therapeutic applications[J]. Med Sci (Paris), 2008, 24(10): 821827.
25. Pennati M, Folini M, Zaffaroni N. Targeting survivin in cancer therapy: fulfilled promises and open questions[J].Carcinogenesis, 2007, 28(6): 11331139.
26. 何滿西, 李耿, 姚有貴, 等. 胰腺癌細胞survivin表達RNAi抑制載體的構(gòu)建及其抑制作用的研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(11): 829834.
27. 姜丹丹, 楊生生, 陳歡, 等. siRNA干擾ski基因的表達對人肝癌HepG2 細胞生物學(xué)功能的影響 [J]. 第二軍醫(yī)大學(xué)學(xué)報, 2008， 29(9): 10251029.
28. 劉世呈, 李靖, 黃小兵, 等. BC047440 siRNA 對肝癌HepG2 細胞增殖抑制及其分子機制的初步探討 [J]. 第三軍醫(yī)大學(xué)學(xué)報, 2007， 29(3): 22072211.
29. 廖維甲, 梅銘惠, 徐靜, 等. 小干擾RNA 抑制肝癌細胞株BEL7402 ICAM1 基因表達的研究 [J]. 中國現(xiàn)代醫(yī)學(xué)雜志, 2006, 16(20): 36653669.
30. 李靜, 樸云峰, 蔣政, 等. siRNA 沉默STAT3 基因?qū)θ烁伟┘毎囊种萍皩ο嚓P(guān)生長調(diào)控基因的調(diào)節(jié) [J]. 世界華人消化雜志, 2007, 15(19): 21012107.
31. 劉權(quán)焰, 劉志蘇, 鄔開朗, 等. MAT2A 基因小干擾RNA誘導(dǎo)人肝癌細胞凋亡的分子機制 [J]. 中國生物化學(xué)與分子生物學(xué)報, 2006, 22(7): 575583.
32. 段瑞紅, 閆歌, 公茂慶, 等. siRNA腺病毒抑制Survivin基因表達誘導(dǎo)肝癌細胞凋亡 [J]. 中國病原生物學(xué)雜志, 2007, 2(5): 321325.
33. 曾桃英, 劉蓓, 王瓊. Livin基因特異性siRNA對肝癌細胞增殖、轉(zhuǎn)移的影響 [J]. 中國現(xiàn)代醫(yī)學(xué)雜志, 2008, 18(24): 35583561, 3565.
34. 楊仕明, 房殿春, 劉愛民, 等. 端粒酶蛋白催化亞單位反義基因?qū)epG2細胞惡性表型的逆轉(zhuǎn)作用 [J]. 中華肝臟病雜志, 2002, 10(2): 9799.
35. 宋文哲, 宋燕, 譚巖, 等. 靶向survivin的反義寡核苷酸聯(lián)合三苯氧胺治療乳腺癌的研究 [J].中國普外基礎(chǔ)與臨床雜志, 2010, 17(9): 922926.
36. 鄭斌, 段體德, 左鐵. VEGFASODN轉(zhuǎn)染對胃癌細胞VEGF表達及生長的抑制作用 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(5): 347351.
37. 劉海威, 程樂, 吳非, 等. 脂質(zhì)體轉(zhuǎn)染survivin反義寡核苷酸對人胰腺癌細胞凋亡的影響 [J].中國普外基礎(chǔ)與臨床雜志, 2010, 17(10): 10561061.
38. 潘克儉, 劉小菁, 楊春蕾, 等. Survivin反義核酸對SMMC7721細胞增殖和凋亡的影響 [J]. 生物醫(yī)學(xué)工程學(xué)雜志, 2006, 23(3): 625629.
  1. 1. Andersen MH, Svane IM, Becker JC, et al. The universal character of the tumorassociated antigen survivin [J]. Clin Cancer Res, 2007, 13(20): 59915994.
  2. 2. Montorsi M, Maggioni M, Falleni M, et al. Survivin gene expression in chronic liver disease and hepatocellular carcinoma[J]. Hepatogastroenterology, 2007, 54(79): 20402044.
  3. 3. Kitamura H, Torigoe T, Honma I, et al. Expression and antigenicity of survivin, an inhibitor of apoptosis family member, in bladder cancer: implications for specific immunotherapy[J]. Urology, 2006, 67(5): 955959.
  4. 4. Ambrosini G, Adida C, Altieri DC. A novel antiapoptosis gene, survivin, expressed in cancer and lymphoma[J]. Nat Med, 1997, 3(8): 917921.
  5. 5. NikolovskaColeska Z, Meagher JL, Jiang S, et al. Interaction of a cyclic, bivalent smac mimetic with the xlinked inhibitor of apoptosis protein[J]. Biochemistry, 2008, 47(37): 98119824.
  6. 6. Colnaghi R, Connell CM, Barrett RM, et al. Separating the antiapoptotic and mitotic roles of survivin[J]. J Biol Chem, 2006, 281(44): 3345033456.
  7. 7. Knauer SK, Bier C, Schlag P, et al. The survivin isoform survivin3B is cytoprotective and can function as a chromosomal passenger complex protein[J]. Cell Cycle, 2007, 6(12): 15021509.
  8. 8. Atlasi Y, Mowla SJ, Ziaee SA. Differential expression of survivin and its splice variants, survivinDeltaEx3 and survivin2B, in bladder cancer[J]. Cancer Detect Prev, 2009, 32(4): 308313.
  9. 9. Suzuki A, Ito T, Kawano H, et al. Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fasmediated cell death[J]. Oncogene, 2000, 19(10): 13461353.
  10. 10. Verdecia MA, Huang H, Dutil E, et al. Structure of the human antiapoptotic protein survivin reveals a dimeric arrangement[J]. Nat Struct Biol, 2006, 7(7): 602608.
  11. 11. Marusawa H, Matsuzawa S, Welsh K, et al. HBXIP functions as a cofactor of survivin in apoptosis suppression[J]. EMBO J, 2003, 22(11): 27292740.
  12. 12. Zhao J, Tenev T, Martins LM, et al. The ubiquitinproteasome pathway regulates survivin degradation in a cell cycledependent manner[J]. J Cell Sci, 2000, 113 (Pt 23): 43634371.
  13. 13. Wolanin K, Piwocka K. Role of survivin in mitosis[J]. Postepy Biochem, 2007, 53(1): 1018.
  14. 14. Suzuki A, Hayashida M, Ito T, et al. Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16（INK4a）and Cdk2/cyclin E complex activation[J]. Oncogene, 2000, 19(29): 32253234.
  15. 15. Mita AC, Mita MM, Nawrocki ST, et al. Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics[J]. Clin Cancer Res, 2008, 14(16): 50005005.
  16. 16. Li YH, Hu CF, Shao Q, et al. Elevated expressions of survivin and VEGF protein are strong independent predictors of survival in advanced nasopharyngeal carcinoma[J]. J Transl Med, 2008, 6: 1.
  17. 17. Ma ACh, Lin R, Chan PK, et al. The role of survivin in angiogenesis during Zebrafish embryonic development[J]. BMC Dev Biol, 2007, 7: 50.
  18. 18. 孔令建, 趙晶, 曲波, 等. Survivin、COX2及VEGF在大腸癌中的表達及與腫瘤微血管密度的關(guān)系 [J]. 世界華人消化雜志, 2009, 17(20): 20482053.
  19. 19. Abe S, Hasegawa M, Yamamoto K, et al. Rapid induction of IAP family proteins and Smac/DIABLO expression after proapoptotic stimulation with doxorubicin in RPMI 8226 multiple myeloma cells[J]. Exp Mol Pathol, 2007, 83(3): 405412.
  20. 20. 管小青, 吳驥, 顧書成, 等. survivin與p53、Ki67在復(fù)發(fā)轉(zhuǎn)移性乳腺癌組織中表達及相關(guān)性研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(3): 290294.
  21. 21. 崔斐, 陳斌, 陳錦章, 等. 凋亡抑制蛋白Survivin和血管內(nèi)皮生長因子在肝細胞癌中的表達及其臨床意義 [J]. 南方醫(yī)科大學(xué)學(xué)報, 2008, 28(5): 761763.
  22. 22. Chao JI, Kuo PC, Hsu TS. Downregulation of survivin in nitric oxideinduced cell growth inhibition and apoptosis of the human lung carcinoma cells[J]. J Biol Chem, 2004, 279(19): 2026720276.
  23. 23. Li F, Ling X. Survivin study: an update of “what is the next wave”?[J]. J Cell Physiol, 2006, 208(3): 476486.
  24. 24. Romagnoli M, Séveno C, Bataille R, et al. Survivin in cancerology: molecular aspects and therapeutic applications[J]. Med Sci (Paris), 2008, 24(10): 821827.
  25. 25. Pennati M, Folini M, Zaffaroni N. Targeting survivin in cancer therapy: fulfilled promises and open questions[J].Carcinogenesis, 2007, 28(6): 11331139.
  26. 26. 何滿西, 李耿, 姚有貴, 等. 胰腺癌細胞survivin表達RNAi抑制載體的構(gòu)建及其抑制作用的研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(11): 829834.
  27. 27. 姜丹丹, 楊生生, 陳歡, 等. siRNA干擾ski基因的表達對人肝癌HepG2 細胞生物學(xué)功能的影響 [J]. 第二軍醫(yī)大學(xué)學(xué)報, 2008， 29(9): 10251029.
  28. 28. 劉世呈, 李靖, 黃小兵, 等. BC047440 siRNA 對肝癌HepG2 細胞增殖抑制及其分子機制的初步探討 [J]. 第三軍醫(yī)大學(xué)學(xué)報, 2007， 29(3): 22072211.
  29. 29. 廖維甲, 梅銘惠, 徐靜, 等. 小干擾RNA 抑制肝癌細胞株BEL7402 ICAM1 基因表達的研究 [J]. 中國現(xiàn)代醫(yī)學(xué)雜志, 2006, 16(20): 36653669.
  30. 30. 李靜, 樸云峰, 蔣政, 等. siRNA 沉默STAT3 基因?qū)θ烁伟┘毎囊种萍皩ο嚓P(guān)生長調(diào)控基因的調(diào)節(jié) [J]. 世界華人消化雜志, 2007, 15(19): 21012107.
  31. 31. 劉權(quán)焰, 劉志蘇, 鄔開朗, 等. MAT2A 基因小干擾RNA誘導(dǎo)人肝癌細胞凋亡的分子機制 [J]. 中國生物化學(xué)與分子生物學(xué)報, 2006, 22(7): 575583.
  32. 32. 段瑞紅, 閆歌, 公茂慶, 等. siRNA腺病毒抑制Survivin基因表達誘導(dǎo)肝癌細胞凋亡 [J]. 中國病原生物學(xué)雜志, 2007, 2(5): 321325.
  33. 33. 曾桃英, 劉蓓, 王瓊. Livin基因特異性siRNA對肝癌細胞增殖、轉(zhuǎn)移的影響 [J]. 中國現(xiàn)代醫(yī)學(xué)雜志, 2008, 18(24): 35583561, 3565.
  34. 34. 楊仕明, 房殿春, 劉愛民, 等. 端粒酶蛋白催化亞單位反義基因?qū)epG2細胞惡性表型的逆轉(zhuǎn)作用 [J]. 中華肝臟病雜志, 2002, 10(2): 9799.
  35. 35. 宋文哲, 宋燕, 譚巖, 等. 靶向survivin的反義寡核苷酸聯(lián)合三苯氧胺治療乳腺癌的研究 [J].中國普外基礎(chǔ)與臨床雜志, 2010, 17(9): 922926.
  36. 36. 鄭斌, 段體德, 左鐵. VEGFASODN轉(zhuǎn)染對胃癌細胞VEGF表達及生長的抑制作用 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(5): 347351.
  37. 37. 劉海威, 程樂, 吳非, 等. 脂質(zhì)體轉(zhuǎn)染survivin反義寡核苷酸對人胰腺癌細胞凋亡的影響 [J].中國普外基礎(chǔ)與臨床雜志, 2010, 17(10): 10561061.
  38. 38. 潘克儉, 劉小菁, 楊春蕾, 等. Survivin反義核酸對SMMC7721細胞增殖和凋亡的影響 [J]. 生物醫(yī)學(xué)工程學(xué)雜志, 2006, 23(3): 625629.