• 1.河北北方學(xué)院研究生院(河北張家口 075000);;
  • 2.解放軍第251醫(yī)院普通外科（河北張家口 075000）;

目的 介紹結(jié)直腸癌Lewis-Selectin轉(zhuǎn)移途徑和西咪替丁抗癌輔助治療的研究進(jìn)展。
方法 收集近年來國內(nèi)、外有關(guān)Lewis-Selectin轉(zhuǎn)移途徑和西咪替丁抗轉(zhuǎn)移輔助治療研究的文獻(xiàn)并作綜述。
結(jié)果 在Lewis抗原,唾液酸化Lewis X（sLeX）在結(jié)直腸癌中表達(dá)陽性率最高，腫瘤細(xì)胞借助細(xì)胞表面sLeX與激活的血管內(nèi)皮細(xì)胞的E-selectin和P-selectin相互作用, 從而促使腫瘤侵襲和轉(zhuǎn)移; 西咪替丁可提高宿主對腫瘤細(xì)胞的免疫反應(yīng)，影響腫瘤新生血管的生成，具有抑制腫瘤生長和轉(zhuǎn)移的重要作用，且對sLeX陽性的結(jié)直腸癌患者的療效要好于陰性者。
結(jié)論 Lewis-Selectin轉(zhuǎn)移途徑是結(jié)直腸癌重要轉(zhuǎn)移途徑之一，西咪替丁對sLeX高水平表達(dá)的結(jié)直腸癌患者有一定的抗轉(zhuǎn)移治療作用。

引用本文： 王首星,尚培中. 結(jié)直腸癌Lewis-Selectin轉(zhuǎn)移途徑與西咪替丁抗癌治療研究進(jìn)展. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(7): 760-764. doi: 復(fù)制

1. 尚培中, 張金江, 劉景章, 等. 基質(zhì)金屬蛋白酶26和唾液酸化LewisX蛋白在乳腺癌中的表達(dá)及其意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(7): 474476.
2. Kobayashi K, Matsumoto S, Morishima T, et al. Cimetidine inhibits cancer cell adhesion to endothelial cells and prevents metastasis by blocking Eselectin expression [J]. Cancer Res, 2000; 60(14): 39783984.
3. Tsuboi K, Asao T, Ide M, et al. α1, 2 fucosylation is a superior predictor of postoperative prognosis for colorectal cancer compared with blood group A, B, or sialyl Lewis X antigen generated within colorectal tumor tissues [J]. Ann Surg Oncol, 2007; 14(6): 18801889.
4. Nonaka M, Ma BY, Murai R, et al. Glycosylationdependent interactions of Ctype lectin DCSIGN with colorectal tumorassociated Lewis glycans impair the function and differentiation of monocytederived dendritic cell [J]. J Immunol, 2008; 180(5): 33473356.
5. BenDavid T, SagiAssif O, Meshel T, et al. The involvement of the sLea selectin ligand in the extravasation of human colorectal carcinoma cells [J]. Immunol Lett, 2008; 116(2): 218224.
6. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells [J]. Nat Immunol, 2003; 4(4): 330336.
7. Morgan ME, van Bilsen JH, Bakker AM, et al. Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans [J]. Hum Immunol, 2005; 66(1): 1320.
8. 李飛飛, 林蓓, 郝瑩瑩, 等. Lewis y抗體對α1, 2巖藻糖轉(zhuǎn)移酶基因轉(zhuǎn)染后卵巢癌細(xì)胞的體外抑制作用 [J]. 細(xì)胞與分子免疫學(xué)雜志, 2008; 24(3): 267269, 273.
9. Zhang Z, Sun P, Liu J, et al. Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth [J]. Biochim Biophys Acta, 2008; 1783(2): 287296.
10. 尚培中, 谷化平. 乳腺癌Lewis X和唾液酸化Lewis X表達(dá)研究 [J]. 中國現(xiàn)代普通外科進(jìn)展, 2005; 8(2): 104106.
11. 尚培中, 谷化平, 孫印臣. 唾液酸化Lewis X 在大腸癌中的表達(dá)研究 [J]. 中華普通外科雜志, 2001; 16(10): 593594.
12. 谷化平, 尚培中, 倪燦榮. Sialy1 Lewis X, CD44v6和Ecadherin 表達(dá)與肝細(xì)胞癌轉(zhuǎn)移和預(yù)后的關(guān)系 [J]. 中華普通外科雜志, 2003; 18(2): 109111.
13. Kawamura Y, Kawashima R , Fukunaga R, et al. Introduction of Sd (a) carbohydrate antigen in gastrointestinal cancer cells eliminates selectin ligands and inhibits metastasis [J]. Cancer Res, 2005; 65(14): 62206227.
14. Malagolini N, Santini D, Chiricolo M, et al. Biosynthesis and expression of the Sda and sialyl Lewis x antigens in normal and cancer colon [J]. Glycobiology, 2007; 17(7): 688697.
15. Mantur M, Koper O, Snarska J, et al. Evaluation of PDGFAB and sPselectin concentrations in relation to platelet count in patients with colorectal cancer before and after surgical treatment [J]. Pol Arch Med Wewn, 2008; 118(6): 345350.
16. ReyesReyes ME, George MD, Roberts JD, et al. PSelectin activates integrinmediated colon carcinoma cell adhesion to fibronectin [J]. Exp Cell Res, 2006; 312(20): 40564069.
17. Uner A, Akcali Z, Unsal D. Serum levels of soluble Eselectin in colorectal cancer [J]. Neoplasma, 2004; 51(4): 269274.
18. DymickaPiekarska V, Kemona H. Does colorectal cancer clinical advancement affect adhesion molecules (sPselectin, sEselectin and ICAM1) concentration? [J]. Thromb Res, 2009; 124(1): 8083.
19. 郎偉思, 王繼見, 張楊眉. Eselectin 在大腸癌的表達(dá)及其在血行轉(zhuǎn)移中的作用初探 [J]. 重慶醫(yī)科大學(xué)學(xué)報, 2009; 34(7): 867869.
20. Kannagi R, Izawa M, Koike T, et al. Carbohydratemediated cell adhesion in cancer metastasis and angiogenesis [J]. Cancer Sci, 2004; 95(5): 377384.
21. Chen AJ, Li Y, Yang GL, et al. Perioperative cimetidine administration enhances tumor infiltration lymphocytes and HLADR expression in colorectal cancer [J]. ChineseGerman Clin Oncol, 2006; 5(1): 4953.
22. 尚培中, 賈國洪, 李曉武, 等. 西咪替丁對大腸癌肝轉(zhuǎn)移的預(yù)防和輔助治療價值 [J/CD]. 中華普外科手術(shù)學(xué)雜志(電子版), 2009; 3(2): 5356.
23. Chihara Y, Fujimoto K, Miyake M, et al. Antitumor effect of cimetidine via inhibiting angiogenesis factors in NbutylN(4hydroxybutyl) nitrosamineinduced mouse and rat bladder carcinogenesis [J]. Oncol Rep, 2009; 22(1): 2328.
24. Bolton E, King J, Morris DL. H2antagonists in the treatment of colon and breast cancer [J]. Semin Cancer Biol, 2000; 10(1): 310.
25. Matsumoto S, Imaeda Y, Umemoto S, et al. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl LewisX and sialyl LewisA epitope expression on tumour cells [J]. Br J Cancer, 2002; 86(2): 161167.
26. Tatokoro M, Fujii Y, Kawakami S, et al. Favorable response to combination treatment of cimetidine, cyclooxygenase2 inhibitor and reninangiotensin system inhibitor in metastatic renal cell carcinoma: Reort of three cases [J]. Int J Uol, 2008; 15(9): 848850.
27. Mathes RW, Malone KE, Daling JR, et al. Relationship between histamine2receptor antagonist medications and risk of invasive breast cancer [J]. Cancer Epidemiol Biomarkers Prev, 2008; 17(1): 6772.
28. Furuta K, Sato S, Miyake T, et al. Antitumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosaminetreated rats [J]. Oncol Rep, 2008; 19(2): 361368.
29. Rajendra S, Mulcahy H, Patchett S, et al. The effect of H2 antagonistson proliferation and apoptosis in human colorectal cancer cell lines [J]. Dig Dis Sci, 2004; 49(10): 16341640.
30. Fujikawa T, Shiraha H, Nakanishi Y, et al. Cimetidine inhibits epidermal growth factorinduced cell signaling [J]. J Gastroenterol Hepatol, 2007; 22(3): 436443.
31. Fukuda M, Kusama K, Sakashita H. Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression [J]. BMC Cancer, 2008; 8(12): 376389.
32. Adams WJ, Morris DL. Shortcourse cimetidine and survival with colorectal cancer [J]. Lancet, 1994; 344 (89398940):17681769.
33. 潘永成, 張壽熙, 丁顯仲, 等. 甲氰咪胍對創(chuàng)傷大鼠的免疫調(diào)節(jié)作用 [J]. 中華實(shí)驗(yàn)外科雜志, 1996; 13(5): 103104.
34. Li Y, Yang GL, Yuan HY, et al. Effects of perioperative cimetidine administration on peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial [J]. Hepatogastroenterology, 2005; 52(62): 504508.
35. Takahashi K, Tanaka S, Ichikawa A. Effect of cimetidine on intratumoral cytokine expression in an experimental tumor [J]. Biochem Biophys Research Commun, 2001; 281(5): 11131119.
36. Asakage M, Tsuno NH, Kitayama J, et al. The effect of cimetidine mainly increases CD4+ cell of peripheral blood T lymphocytes [J]. Gan To Kagaku Ryoho, 2005; 32(11): 15761577.
37. Bobek V, Boubelik M, Kovarík J, et al. Inhibition of adhesion breast cancer cells by anticoagulant drugs and cimetidine [J]. Neoplasma, 2003; 50(2): 148151.
38. Tozawa K, Okamoto T, Kawai N, et al. Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma [J]. Kidney Int, 2005; 67(4): 13911396.
39. Hansbrough JF, ZapataSirvent RL, Bender EM. Prevention of alterations in postoperative lymphocyte subpopulations by cimetidine and ibuprofen [J]. Am J Surg, 1986; 151(2): 249255.
40. Lefranc F, Yeaton P, Brotchi J, et al. Cimetidine, an unexpected antitumor agent, and its potential for the treatment of glioblastoma (review) [J]. Int J Oncol, 2006; 28(5): 10211030.
41. Kawase J, Ozawa S, Kobayashi K, et al. Increase in Eselectin expression in umbilical vein endothelial cells by anticancer drugs and inhibition by cimetidine [J]. Oncol Rep, 2009; 22(6): 12931297.
42. 尚培中, 賈國洪, 苗建軍, 等. 西咪替丁預(yù)防大腸癌復(fù)發(fā)轉(zhuǎn)移臨床療效觀察 [J/CD]. 中華普通外科學(xué)文獻(xiàn)(電子版), 2009; 3(1): 2730.
  1. 1. 尚培中, 張金江, 劉景章, 等. 基質(zhì)金屬蛋白酶26和唾液酸化LewisX蛋白在乳腺癌中的表達(dá)及其意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(7): 474476.
  2. 2. Kobayashi K, Matsumoto S, Morishima T, et al. Cimetidine inhibits cancer cell adhesion to endothelial cells and prevents metastasis by blocking Eselectin expression [J]. Cancer Res, 2000; 60(14): 39783984.
  3. 3. Tsuboi K, Asao T, Ide M, et al. α1, 2 fucosylation is a superior predictor of postoperative prognosis for colorectal cancer compared with blood group A, B, or sialyl Lewis X antigen generated within colorectal tumor tissues [J]. Ann Surg Oncol, 2007; 14(6): 18801889.
  4. 4. Nonaka M, Ma BY, Murai R, et al. Glycosylationdependent interactions of Ctype lectin DCSIGN with colorectal tumorassociated Lewis glycans impair the function and differentiation of monocytederived dendritic cell [J]. J Immunol, 2008; 180(5): 33473356.
  5. 5. BenDavid T, SagiAssif O, Meshel T, et al. The involvement of the sLea selectin ligand in the extravasation of human colorectal carcinoma cells [J]. Immunol Lett, 2008; 116(2): 218224.
  6. 6. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells [J]. Nat Immunol, 2003; 4(4): 330336.
  7. 7. Morgan ME, van Bilsen JH, Bakker AM, et al. Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans [J]. Hum Immunol, 2005; 66(1): 1320.
  8. 8. 李飛飛, 林蓓, 郝瑩瑩, 等. Lewis y抗體對α1, 2巖藻糖轉(zhuǎn)移酶基因轉(zhuǎn)染后卵巢癌細(xì)胞的體外抑制作用 [J]. 細(xì)胞與分子免疫學(xué)雜志, 2008; 24(3): 267269, 273.
  9. 9. Zhang Z, Sun P, Liu J, et al. Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth [J]. Biochim Biophys Acta, 2008; 1783(2): 287296.
  10. 10. 尚培中, 谷化平. 乳腺癌Lewis X和唾液酸化Lewis X表達(dá)研究 [J]. 中國現(xiàn)代普通外科進(jìn)展, 2005; 8(2): 104106.
  11. 11. 尚培中, 谷化平, 孫印臣. 唾液酸化Lewis X 在大腸癌中的表達(dá)研究 [J]. 中華普通外科雜志, 2001; 16(10): 593594.
  12. 12. 谷化平, 尚培中, 倪燦榮. Sialy1 Lewis X, CD44v6和Ecadherin 表達(dá)與肝細(xì)胞癌轉(zhuǎn)移和預(yù)后的關(guān)系 [J]. 中華普通外科雜志, 2003; 18(2): 109111.
  13. 13. Kawamura Y, Kawashima R , Fukunaga R, et al. Introduction of Sd (a) carbohydrate antigen in gastrointestinal cancer cells eliminates selectin ligands and inhibits metastasis [J]. Cancer Res, 2005; 65(14): 62206227.
  14. 14. Malagolini N, Santini D, Chiricolo M, et al. Biosynthesis and expression of the Sda and sialyl Lewis x antigens in normal and cancer colon [J]. Glycobiology, 2007; 17(7): 688697.
  15. 15. Mantur M, Koper O, Snarska J, et al. Evaluation of PDGFAB and sPselectin concentrations in relation to platelet count in patients with colorectal cancer before and after surgical treatment [J]. Pol Arch Med Wewn, 2008; 118(6): 345350.
  16. 16. ReyesReyes ME, George MD, Roberts JD, et al. PSelectin activates integrinmediated colon carcinoma cell adhesion to fibronectin [J]. Exp Cell Res, 2006; 312(20): 40564069.
  17. 17. Uner A, Akcali Z, Unsal D. Serum levels of soluble Eselectin in colorectal cancer [J]. Neoplasma, 2004; 51(4): 269274.
  18. 18. DymickaPiekarska V, Kemona H. Does colorectal cancer clinical advancement affect adhesion molecules (sPselectin, sEselectin and ICAM1) concentration? [J]. Thromb Res, 2009; 124(1): 8083.
  19. 19. 郎偉思, 王繼見, 張楊眉. Eselectin 在大腸癌的表達(dá)及其在血行轉(zhuǎn)移中的作用初探 [J]. 重慶醫(yī)科大學(xué)學(xué)報, 2009; 34(7): 867869.
  20. 20. Kannagi R, Izawa M, Koike T, et al. Carbohydratemediated cell adhesion in cancer metastasis and angiogenesis [J]. Cancer Sci, 2004; 95(5): 377384.
  21. 21. Chen AJ, Li Y, Yang GL, et al. Perioperative cimetidine administration enhances tumor infiltration lymphocytes and HLADR expression in colorectal cancer [J]. ChineseGerman Clin Oncol, 2006; 5(1): 4953.
  22. 22. 尚培中, 賈國洪, 李曉武, 等. 西咪替丁對大腸癌肝轉(zhuǎn)移的預(yù)防和輔助治療價值 [J/CD]. 中華普外科手術(shù)學(xué)雜志(電子版), 2009; 3(2): 5356.
  23. 23. Chihara Y, Fujimoto K, Miyake M, et al. Antitumor effect of cimetidine via inhibiting angiogenesis factors in NbutylN(4hydroxybutyl) nitrosamineinduced mouse and rat bladder carcinogenesis [J]. Oncol Rep, 2009; 22(1): 2328.
  24. 24. Bolton E, King J, Morris DL. H2antagonists in the treatment of colon and breast cancer [J]. Semin Cancer Biol, 2000; 10(1): 310.
  25. 25. Matsumoto S, Imaeda Y, Umemoto S, et al. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl LewisX and sialyl LewisA epitope expression on tumour cells [J]. Br J Cancer, 2002; 86(2): 161167.
  26. 26. Tatokoro M, Fujii Y, Kawakami S, et al. Favorable response to combination treatment of cimetidine, cyclooxygenase2 inhibitor and reninangiotensin system inhibitor in metastatic renal cell carcinoma: Reort of three cases [J]. Int J Uol, 2008; 15(9): 848850.
  27. 27. Mathes RW, Malone KE, Daling JR, et al. Relationship between histamine2receptor antagonist medications and risk of invasive breast cancer [J]. Cancer Epidemiol Biomarkers Prev, 2008; 17(1): 6772.
  28. 28. Furuta K, Sato S, Miyake T, et al. Antitumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosaminetreated rats [J]. Oncol Rep, 2008; 19(2): 361368.
  29. 29. Rajendra S, Mulcahy H, Patchett S, et al. The effect of H2 antagonistson proliferation and apoptosis in human colorectal cancer cell lines [J]. Dig Dis Sci, 2004; 49(10): 16341640.
  30. 30. Fujikawa T, Shiraha H, Nakanishi Y, et al. Cimetidine inhibits epidermal growth factorinduced cell signaling [J]. J Gastroenterol Hepatol, 2007; 22(3): 436443.
  31. 31. Fukuda M, Kusama K, Sakashita H. Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression [J]. BMC Cancer, 2008; 8(12): 376389.
  32. 32. Adams WJ, Morris DL. Shortcourse cimetidine and survival with colorectal cancer [J]. Lancet, 1994; 344 (89398940):17681769.
  33. 33. 潘永成, 張壽熙, 丁顯仲, 等. 甲氰咪胍對創(chuàng)傷大鼠的免疫調(diào)節(jié)作用 [J]. 中華實(shí)驗(yàn)外科雜志, 1996; 13(5): 103104.
  34. 34. Li Y, Yang GL, Yuan HY, et al. Effects of perioperative cimetidine administration on peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial [J]. Hepatogastroenterology, 2005; 52(62): 504508.
  35. 35. Takahashi K, Tanaka S, Ichikawa A. Effect of cimetidine on intratumoral cytokine expression in an experimental tumor [J]. Biochem Biophys Research Commun, 2001; 281(5): 11131119.
  36. 36. Asakage M, Tsuno NH, Kitayama J, et al. The effect of cimetidine mainly increases CD4+ cell of peripheral blood T lymphocytes [J]. Gan To Kagaku Ryoho, 2005; 32(11): 15761577.
  37. 37. Bobek V, Boubelik M, Kovarík J, et al. Inhibition of adhesion breast cancer cells by anticoagulant drugs and cimetidine [J]. Neoplasma, 2003; 50(2): 148151.
  38. 38. Tozawa K, Okamoto T, Kawai N, et al. Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma [J]. Kidney Int, 2005; 67(4): 13911396.
  39. 39. Hansbrough JF, ZapataSirvent RL, Bender EM. Prevention of alterations in postoperative lymphocyte subpopulations by cimetidine and ibuprofen [J]. Am J Surg, 1986; 151(2): 249255.
  40. 40. Lefranc F, Yeaton P, Brotchi J, et al. Cimetidine, an unexpected antitumor agent, and its potential for the treatment of glioblastoma (review) [J]. Int J Oncol, 2006; 28(5): 10211030.
  41. 41. Kawase J, Ozawa S, Kobayashi K, et al. Increase in Eselectin expression in umbilical vein endothelial cells by anticancer drugs and inhibition by cimetidine [J]. Oncol Rep, 2009; 22(6): 12931297.
  42. 42. 尚培中, 賈國洪, 苗建軍, 等. 西咪替丁預(yù)防大腸癌復(fù)發(fā)轉(zhuǎn)移臨床療效觀察 [J/CD]. 中華普通外科學(xué)文獻(xiàn)(電子版), 2009; 3(1): 2730.