• 1.四川大學華西醫(yī)院普外三科(成都610041);;
  • 2.四川大學華西醫(yī)院中西醫(yī)結(jié)合科;

目的　 介紹腫瘤壞死因子相關(guān)凋亡誘導(dǎo)配體(TRAIL)及其受體在胃癌的研究現(xiàn)狀。
方法 　檢索PUB-MEDLINE和中國期刊全文數(shù)據(jù)庫(CJFD)，綜述國內(nèi)、外近年關(guān)于TRAIL及其受體在胃癌的相關(guān)研究文獻。
結(jié)果 　TRAIL在胃癌組織表達水平報道情況差異較大，但其與胃癌的分化程度和浸潤、轉(zhuǎn)移情況密切相關(guān)。其受體DR4及DR5在胃癌組織均表達陽性，而DcR1及DcR2在胃癌組織亦有表達陽性的報道。caspase-3、caspase-8和survivin對胃癌TRAIL信號通路有重要調(diào)節(jié)作用。5-氮-2′-雜脫氧胞苷、阿霉素、5-氟尿嘧啶、α-生育酚及X射線照射可協(xié)同增強TRAIL對胃癌細胞的凋亡誘導(dǎo)作用。
結(jié)論 　胃癌可能適合TRAIL靶向治療，但其作用機理較為復(fù)雜并受到多因素影響。尚有如何有效增強和調(diào)控TRAIL凋亡誘導(dǎo)作用及TRAIL有何潛在毒性等諸多問題亟待研究。

引用本文： 陳心足,姜坤,胡建昆. TRAIL信號通路在胃癌的研究現(xiàn)狀. 中國普外基礎(chǔ)與臨床雜志, 2007, 14(3): 371-375. doi: 復(fù)制

1. Gores GJ, Kaufmann SH. Is TRAIL hepatotoxic? [J]. Hepatology， 2001; 34(1)∶3.
2. Parkin DM. Global cancer statistics in the year 2000 [J]. Lancet Oncol， 2001; 2(9)∶533.
3. 孫秀娣, 牧人, 周有尚, 等. 中國胃癌死亡率20年變化情況分析及其發(fā)展趨勢預(yù)測 [J]. 中華腫瘤雜志, 2004; 26(1)∶4.
4. Wiley SR, Schooley K, Smolak PJ, et al. Identification and characterization of a new member of the TNF family that induces apoptosis [J]. Immunity， 1995; 3(6)∶673.
5. Kimberley FC, Screaton GR. Following a TRAIL: update on a ligand and its five receptors [J]. Cell Res， 2004; 14(5)∶359.
6. Sheridan JP, Marsters SA, Pitti RM, et al. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors [J]. Science， 1997; 277(5327)∶818.
7. 僧靖靜， 張云漢， 高冬玲. TRAIL、 Survivin mRNA表達與胃癌凋亡發(fā)生的相關(guān)關(guān)系 [J]. 河南大學學報(醫(yī)學科學版)， 2005; 24(1)∶25.
8. Yoo NJ, Kim HS, Kim SY, et al. Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas [J]. APMIS， 2003; 111(3)∶382.
9. Sinicrope FA, Penington RC, Tang XM. Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis is inhibited by Bcl-2 but restored by the small molecule Bcl-2 inhibitor, HA 14-1, in human colon cancer cells [J]. Clin Cancer Res， 2004; 10(24)∶8284.
10. Koyama S, Koike N, Adachi S. Expression of TNF-related apoptosis-inducing ligand (TRAIL) and its receptors in gastric carcinoma and tumor-infiltrating lymphocytes: a possible mechanism of immune evasion of the tumor [J]. J Cancer Res Clin Oncol， 2002; 128(2)∶73.
11. 張淑紅, 周世慶, 真巖波, 等. 胃癌細胞Trail表達與細胞凋亡檢測結(jié)果分析 [J]. 山東醫(yī)藥, 2002; 42(21)∶27.
12. 劉勝雄, 湯明, 吳飛躍. TRAIL在胃癌中的表達及其意義 [J]. 中國普通外科雜志, 2005; 14(10)∶789.
13. 程文芳, 易粹瓊. 腫瘤壞死因子相關(guān)凋亡誘導(dǎo)配體的受體在胃癌中的表達 [J]. 中華內(nèi)科雜志, 2003; 42(2)∶118.
14. Kuraoka K, Matsumura S, Sanada Y, et al. A single nucleotide polymorphism in the extracellular domain of TRAIL receptor DR4 at nucleotide 626 in gastric cancer patients in Japan [J]. Oncol Rep， 2005; 14(2)∶465.
15. Park WS, Lee JH, Shin MS, et al. Inactivating mutations of KILLER/DR5 gene in gastric cancers [J]. Gastroenterology， 2001; 121(5)∶1219.
16. 張汝鋼, 房殿春, 楊柳芹, 等. 5-Aza-CdR增強TRAIL對胃癌細胞的抗瘤活性與caspase-8表達的關(guān)系 [J]. 第三軍醫(yī)大學學報, 2005; 27(2)∶95.
17. Harada K, Toyooka S, Shivapurkar N, et al. Deregulation of caspase 8 and 10 expression in pediatric tumors and cell lines [J]. Cancer Res， 2002; 62(20)∶5897.
18. Zuzak TJ, Steinhoff DF, Sutton LN, et al. Loss of caspase-8 mRNA expression is common in childhood primitive neuroectodermal brain tumour/medulloblastoma [J]. Eur J Cancer， 2002; 38(1)∶83.
19. Fulda S, Kufer MU, Meyer E, et al. Sensitization for death receptor-or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer [J]. Oncogene， 2001; 20(41)∶5865.
20. 張汝鋼, 房殿春, 楊柳芹, 等. 5-Aza-CdR可提高TRAIL對胃癌細胞Kato3的抗瘤活性 [J]. 重慶醫(yī)學, 2003; 32(9)∶1141.
21. 張汝鋼, 房殿春, 楊柳芹, 等. 胃癌細胞對TRAIL的敏感性與caspase-8基因甲基化狀態(tài)的關(guān)系 [J]. 第三軍醫(yī)大學學報, 2004; 26(2)∶95.
22. Kanehara I, Nakata B, Hirakawa K. Caspase-8 is scarcely silenced and its activity is well correlated with the anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand in gastric cancer cells [J]. Oncol Rep， 2005; 14(5)∶1249.
23. 楊柳芹, 房殿春, 張汝鋼, 等. 胃癌細胞bcl-2和Caspase3的表達對TRAIL抗瘤作用的影響 [J]. 重慶醫(yī)學, 2003; 32(9)∶1132.
24. Yang LQ, Fang DC, Wang RQ, et al. Effect of NF-kappaB, survivin, Bcl-2 and Caspase3 on apoptosis of gastric cancer cells induced by tumor necrosis factor related apoptosis inducing ligand [J]. World J Gastroenterol， 2004; 10(1)∶22.
25. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma [J]. Nat Med， 1997; 3(8)∶917.
26. 楊柳芹, 房殿春. 胃癌細胞NF-κB和survivin的表達對TRAIL抗瘤作用的影響 [J]. 第三軍醫(yī)大學學報, 2004; 26(7)∶584.
27. 程文芳, 易粹瓊. 死亡配體TRAIL誘導(dǎo)胃癌細胞凋亡的研究 [J]. 中華消化內(nèi)鏡雜志, 2002; 19(4)∶229.
28. 程文芳, 易粹瓊. 腫瘤壞死因子相關(guān)凋亡誘導(dǎo)配體誘導(dǎo)人胃癌耐藥細胞凋亡的研究 [J]. 中華消化雜志, 2003; 23(10)∶590.
29. Nam SY, Jung GA, Hur GC, et al. Upregulation of FLIP(S) by Akt, a possible inhibition mechanism of TRAIL-induced apoptosis in human gastric cancers [J]. Cancer Sci， 2003; 94(12)∶1066.
30. 僧靖靜, 張云漢, 高冬玲. TRAIL聯(lián)合化療藥物誘導(dǎo)人胃癌細胞系BGC-823凋亡觀察 [J]. 鄭州大學學報(醫(yī)學版), 2005; 40(3)∶442.
31. Anderson K, Simmons-Menchaca M, Lawson KA, et al. Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA [J]. Cancer Res， 2004; 64(12)∶4263.
32. Tomasetti M, Rippo MR, Alleva R, et al. Alpha-tocopheryl succinate and TRAIL selectively synergise in induction of apoptosis in human malignant mesothelioma cells [J]. Br J Cancer， 2004; 90(8)∶1644.
33. 楊柳芹, 房殿春. α-生育酚對TRAIL誘導(dǎo)胃癌細胞凋亡的影響及機制 [J]. 　解放軍醫(yī)學雜志, 2005; 30(9)∶779.
34. Hamasu T, Inanami O, Asanuma T, et al. Enhanced induction of apoptosis by combined treatment of human carcinoma cells with X rays and death receptor agonists [J]. J Radiat Res, 2005; 46(1)∶103.
35. 王正兵, 賈筱琴, 陳兵, 等. TRAIL真核表達質(zhì)粒的構(gòu)建及抑制肝癌生長的實驗研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2005; 12（3）∶261.
36. 公偉， 劉軍， 梁飛， 等. TRAIL受體在胰腺癌中的表達 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(5)∶521.
  1. 1. Gores GJ, Kaufmann SH. Is TRAIL hepatotoxic? [J]. Hepatology， 2001; 34(1)∶3.
  2. 2. Parkin DM. Global cancer statistics in the year 2000 [J]. Lancet Oncol， 2001; 2(9)∶533.
  3. 3. 孫秀娣, 牧人, 周有尚, 等. 中國胃癌死亡率20年變化情況分析及其發(fā)展趨勢預(yù)測 [J]. 中華腫瘤雜志, 2004; 26(1)∶4.
  4. 4. Wiley SR, Schooley K, Smolak PJ, et al. Identification and characterization of a new member of the TNF family that induces apoptosis [J]. Immunity， 1995; 3(6)∶673.
  5. 5. Kimberley FC, Screaton GR. Following a TRAIL: update on a ligand and its five receptors [J]. Cell Res， 2004; 14(5)∶359.
  6. 6. Sheridan JP, Marsters SA, Pitti RM, et al. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors [J]. Science， 1997; 277(5327)∶818.
  7. 7. 僧靖靜， 張云漢， 高冬玲. TRAIL、 Survivin mRNA表達與胃癌凋亡發(fā)生的相關(guān)關(guān)系 [J]. 河南大學學報(醫(yī)學科學版)， 2005; 24(1)∶25.
  8. 8. Yoo NJ, Kim HS, Kim SY, et al. Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas [J]. APMIS， 2003; 111(3)∶382.
  9. 9. Sinicrope FA, Penington RC, Tang XM. Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis is inhibited by Bcl-2 but restored by the small molecule Bcl-2 inhibitor, HA 14-1, in human colon cancer cells [J]. Clin Cancer Res， 2004; 10(24)∶8284.
  10. 10. Koyama S, Koike N, Adachi S. Expression of TNF-related apoptosis-inducing ligand (TRAIL) and its receptors in gastric carcinoma and tumor-infiltrating lymphocytes: a possible mechanism of immune evasion of the tumor [J]. J Cancer Res Clin Oncol， 2002; 128(2)∶73.
  11. 11. 張淑紅, 周世慶, 真巖波, 等. 胃癌細胞Trail表達與細胞凋亡檢測結(jié)果分析 [J]. 山東醫(yī)藥, 2002; 42(21)∶27.
  12. 12. 劉勝雄, 湯明, 吳飛躍. TRAIL在胃癌中的表達及其意義 [J]. 中國普通外科雜志, 2005; 14(10)∶789.
  13. 13. 程文芳, 易粹瓊. 腫瘤壞死因子相關(guān)凋亡誘導(dǎo)配體的受體在胃癌中的表達 [J]. 中華內(nèi)科雜志, 2003; 42(2)∶118.
  14. 14. Kuraoka K, Matsumura S, Sanada Y, et al. A single nucleotide polymorphism in the extracellular domain of TRAIL receptor DR4 at nucleotide 626 in gastric cancer patients in Japan [J]. Oncol Rep， 2005; 14(2)∶465.
  15. 15. Park WS, Lee JH, Shin MS, et al. Inactivating mutations of KILLER/DR5 gene in gastric cancers [J]. Gastroenterology， 2001; 121(5)∶1219.
  16. 16. 張汝鋼, 房殿春, 楊柳芹, 等. 5-Aza-CdR增強TRAIL對胃癌細胞的抗瘤活性與caspase-8表達的關(guān)系 [J]. 第三軍醫(yī)大學學報, 2005; 27(2)∶95.
  17. 17. Harada K, Toyooka S, Shivapurkar N, et al. Deregulation of caspase 8 and 10 expression in pediatric tumors and cell lines [J]. Cancer Res， 2002; 62(20)∶5897.
  18. 18. Zuzak TJ, Steinhoff DF, Sutton LN, et al. Loss of caspase-8 mRNA expression is common in childhood primitive neuroectodermal brain tumour/medulloblastoma [J]. Eur J Cancer， 2002; 38(1)∶83.
  19. 19. Fulda S, Kufer MU, Meyer E, et al. Sensitization for death receptor-or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer [J]. Oncogene， 2001; 20(41)∶5865.
  20. 20. 張汝鋼, 房殿春, 楊柳芹, 等. 5-Aza-CdR可提高TRAIL對胃癌細胞Kato3的抗瘤活性 [J]. 重慶醫(yī)學, 2003; 32(9)∶1141.
  21. 21. 張汝鋼, 房殿春, 楊柳芹, 等. 胃癌細胞對TRAIL的敏感性與caspase-8基因甲基化狀態(tài)的關(guān)系 [J]. 第三軍醫(yī)大學學報, 2004; 26(2)∶95.
  22. 22. Kanehara I, Nakata B, Hirakawa K. Caspase-8 is scarcely silenced and its activity is well correlated with the anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand in gastric cancer cells [J]. Oncol Rep， 2005; 14(5)∶1249.
  23. 23. 楊柳芹, 房殿春, 張汝鋼, 等. 胃癌細胞bcl-2和Caspase3的表達對TRAIL抗瘤作用的影響 [J]. 重慶醫(yī)學, 2003; 32(9)∶1132.
  24. 24. Yang LQ, Fang DC, Wang RQ, et al. Effect of NF-kappaB, survivin, Bcl-2 and Caspase3 on apoptosis of gastric cancer cells induced by tumor necrosis factor related apoptosis inducing ligand [J]. World J Gastroenterol， 2004; 10(1)∶22.
  25. 25. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma [J]. Nat Med， 1997; 3(8)∶917.
  26. 26. 楊柳芹, 房殿春. 胃癌細胞NF-κB和survivin的表達對TRAIL抗瘤作用的影響 [J]. 第三軍醫(yī)大學學報, 2004; 26(7)∶584.
  27. 27. 程文芳, 易粹瓊. 死亡配體TRAIL誘導(dǎo)胃癌細胞凋亡的研究 [J]. 中華消化內(nèi)鏡雜志, 2002; 19(4)∶229.
  28. 28. 程文芳, 易粹瓊. 腫瘤壞死因子相關(guān)凋亡誘導(dǎo)配體誘導(dǎo)人胃癌耐藥細胞凋亡的研究 [J]. 中華消化雜志, 2003; 23(10)∶590.
  29. 29. Nam SY, Jung GA, Hur GC, et al. Upregulation of FLIP(S) by Akt, a possible inhibition mechanism of TRAIL-induced apoptosis in human gastric cancers [J]. Cancer Sci， 2003; 94(12)∶1066.
  30. 30. 僧靖靜, 張云漢, 高冬玲. TRAIL聯(lián)合化療藥物誘導(dǎo)人胃癌細胞系BGC-823凋亡觀察 [J]. 鄭州大學學報(醫(yī)學版), 2005; 40(3)∶442.
  31. 31. Anderson K, Simmons-Menchaca M, Lawson KA, et al. Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA [J]. Cancer Res， 2004; 64(12)∶4263.
  32. 32. Tomasetti M, Rippo MR, Alleva R, et al. Alpha-tocopheryl succinate and TRAIL selectively synergise in induction of apoptosis in human malignant mesothelioma cells [J]. Br J Cancer， 2004; 90(8)∶1644.
  33. 33. 楊柳芹, 房殿春. α-生育酚對TRAIL誘導(dǎo)胃癌細胞凋亡的影響及機制 [J]. 　解放軍醫(yī)學雜志, 2005; 30(9)∶779.
  34. 34. Hamasu T, Inanami O, Asanuma T, et al. Enhanced induction of apoptosis by combined treatment of human carcinoma cells with X rays and death receptor agonists [J]. J Radiat Res, 2005; 46(1)∶103.
  35. 35. 王正兵, 賈筱琴, 陳兵, 等. TRAIL真核表達質(zhì)粒的構(gòu)建及抑制肝癌生長的實驗研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2005; 12（3）∶261.
  36. 36. 公偉， 劉軍， 梁飛， 等. TRAIL受體在胰腺癌中的表達 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(5)∶521.