劉偉 1 , 安杰 2 , 張超 1 , 劉占奎 1
  • 1.第三軍醫(yī)大學(xué)西南醫(yī)院普外科(重慶 400038);;
  • 2.白求恩國際和平醫(yī)院病理科(石家莊050082);

目的　探討塞來昔布對(duì)體外培養(yǎng)的結(jié)腸癌細(xì)胞生長及裸鼠肝轉(zhuǎn)移瘤的影響。方法　以人結(jié)腸癌細(xì)胞株HT-29（COX-2高表達(dá)）和HCT-116（COX-2低表達(dá)）為研究對(duì)象，采用噻唑藍(lán)（MTT）比色法檢測塞來昔布對(duì)2種細(xì)胞的增殖抑制效應(yīng)，應(yīng)用流式細(xì)胞術(shù)檢測2種細(xì)胞的周期分布情況； 將2種細(xì)胞接種裸鼠，觀察其肝轉(zhuǎn)移瘤形成情況。結(jié)果?、偃麃砦舨紝?duì)人結(jié)腸癌細(xì)胞株生長的抑制作用呈時(shí)間、劑量依賴性效應(yīng)（P＜0.05, P＜0.01），且對(duì)HT-29細(xì)胞的作用強(qiáng)于HCT-116細(xì)胞（P＜0.05）。②塞來昔布可改變結(jié)腸癌細(xì)胞株細(xì)胞周期的分布，明顯降低其增殖指數(shù)。③塞來昔布具有明顯的抑制裸鼠肝轉(zhuǎn)移瘤生長的作用。結(jié)論　塞來昔布可能通過抑制COX-2酶活性而抑制結(jié)腸癌細(xì)胞的分裂和增殖，誘導(dǎo)其凋亡，干預(yù)結(jié)腸癌的轉(zhuǎn)移與復(fù)發(fā)。

引用本文： 劉偉,安杰,張超,劉占奎. 塞來昔布對(duì)人結(jié)腸癌細(xì)胞生長及裸鼠肝轉(zhuǎn)移瘤形成的影響. 中國普外基礎(chǔ)與臨床雜志, 2006, 13(6): 693-697. doi: 復(fù)制

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1. 　Tomozawa S, Tsuno NH, Sunami E, et al. Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially haematogenous metastasis, of colorectal cancer [Ｊ]. Cancer，2000; 83(3)∶ 324.
2. 　Kakiuchi Y, Tsuji S, Tsujii M, et al. Cyclooxygenase-2 activity altered the cell-surface carbohydrate antigens on colon cancer cells and enhanced liver metastasis [Ｊ]. Cancer Res， 2002; 62(5)∶1567.
3. 　DuBois RN, Radhika A, Reddy BS, et al. Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors [Ｊ]. Gastroenterology, 1996; 110(4)∶1259.
4. 　Williams CS, Luongo C, Radhika A, et al. Elevated cyclooxygenase-2 levels in Min mouse adenomas [Ｊ]. Gastroenterology， 1996; 111(4)∶1134.
5. 　Takeuchi K, Tanaka A, Ohno R, et al. Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage [Ｊ]. J Physiol Pharmacol， 2003; 54(Suppl 4)∶165.
6. 　 Herschman HR. Regulation of prostaglandin synthase-1 and prostaglandin synthase-2 [Ｊ]. Cancer Metastasis Rev， 1994; 13(3－4)∶241.
7. 　Shattuck-Brandt RL, Varilek GW, Radhika A, et al. Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice [Ｊ]. Gastroenterology. 2000; 118(8)∶337.
8. 　Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology [Ｊ]. Annu Rev Biochem， 2000; 69∶145.
9. 　Pyrko P, Soriano N, Kardosh A, et al. Downregulation of survivn expression and concomitant induction of apoptosis by celecoxib and its non-cyclooxygenase-2-inhibitory analog, dimethyl-celecoxib (DMC), in tumor cells in vitro and in vivo [Ｊ]. Mol Cancer, 2006; 5∶19.
10. 　朱建民, 曾　明. 環(huán)氧化酶和非甾體類消炎藥 [Ｊ]. 中國新藥與臨床雜志， 2001; 20（3）∶208.
11. 　Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2 [Ｊ]. Cell, 1995; 83(3)∶493.
12. 　Weber A, Casini A, Heine A, et al. Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition [Ｊ]. J Med Chem， 2004; 47(3)∶550.
13. 　Momin RA, De Witt DL, Nair MG. Inhibition of cyclooxygenase (COX) enzymes by compounds from Daucus carota L. Seeds [Ｊ]. Phytother Res, 2003; 17(8)∶976.
14. 　Liu W, Chen Y, Wang W, et al. Combination of radiation and celebrex (celecoxib) reduce mammary and lung tumor growth [Ｊ]. Am J Clin Oncol, 2003; 26(4)∶S103.
15. 　Jacoby RF, Cole CE, Tutsch K, et al. Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos [Ｊ]. Cancer Res, 2000; 60(7)∶1864.
16. 　吳高松, 劉正人, 鄒聲泉, 等. 塞來昔布(celecoxib)通過前列腺素E2途徑影響膽管癌細(xì)胞株生長和凋亡 [Ｊ]. 外科理論與實(shí)踐, 2003; 8(2)∶137.
17. 　Gately S. The contribution of cyclooxygenase-2 to tumor angiogenesis [Ｊ]. Cancer Metastasis Rev, 2001； 19(1－2)∶19.
18. 　Wu GS, Wang JH, Liu ZY, et al. Expression of cyclooxygenase-1 and -2 in extra-hepatic cholangiocarcinoma [Ｊ]. HBPD INT, 2002; 1(3)∶429.
19. 　Yao M, Kargman S, Lam EC, et al. Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice [Ｊ]. Cancer Res, 2003; 63(3)∶586.
  1. 1. 　Tomozawa S, Tsuno NH, Sunami E, et al. Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially haematogenous metastasis, of colorectal cancer [Ｊ]. Cancer，2000; 83(3)∶ 324.
  2. 2. 　Kakiuchi Y, Tsuji S, Tsujii M, et al. Cyclooxygenase-2 activity altered the cell-surface carbohydrate antigens on colon cancer cells and enhanced liver metastasis [Ｊ]. Cancer Res， 2002; 62(5)∶1567.
  3. 3. 　DuBois RN, Radhika A, Reddy BS, et al. Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors [Ｊ]. Gastroenterology, 1996; 110(4)∶1259.
  4. 4. 　Williams CS, Luongo C, Radhika A, et al. Elevated cyclooxygenase-2 levels in Min mouse adenomas [Ｊ]. Gastroenterology， 1996; 111(4)∶1134.
  5. 5. 　Takeuchi K, Tanaka A, Ohno R, et al. Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage [Ｊ]. J Physiol Pharmacol， 2003; 54(Suppl 4)∶165.
  6. 6. 　 Herschman HR. Regulation of prostaglandin synthase-1 and prostaglandin synthase-2 [Ｊ]. Cancer Metastasis Rev， 1994; 13(3－4)∶241.
  7. 7. 　Shattuck-Brandt RL, Varilek GW, Radhika A, et al. Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice [Ｊ]. Gastroenterology. 2000; 118(8)∶337.
  8. 8. 　Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology [Ｊ]. Annu Rev Biochem， 2000; 69∶145.
  9. 9. 　Pyrko P, Soriano N, Kardosh A, et al. Downregulation of survivn expression and concomitant induction of apoptosis by celecoxib and its non-cyclooxygenase-2-inhibitory analog, dimethyl-celecoxib (DMC), in tumor cells in vitro and in vivo [Ｊ]. Mol Cancer, 2006; 5∶19.
  10. 10. 　朱建民, 曾　明. 環(huán)氧化酶和非甾體類消炎藥 [Ｊ]. 中國新藥與臨床雜志， 2001; 20（3）∶208.
  11. 11. 　Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2 [Ｊ]. Cell, 1995; 83(3)∶493.
  12. 12. 　Weber A, Casini A, Heine A, et al. Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition [Ｊ]. J Med Chem， 2004; 47(3)∶550.
  13. 13. 　Momin RA, De Witt DL, Nair MG. Inhibition of cyclooxygenase (COX) enzymes by compounds from Daucus carota L. Seeds [Ｊ]. Phytother Res, 2003; 17(8)∶976.
  14. 14. 　Liu W, Chen Y, Wang W, et al. Combination of radiation and celebrex (celecoxib) reduce mammary and lung tumor growth [Ｊ]. Am J Clin Oncol, 2003; 26(4)∶S103.
  15. 15. 　Jacoby RF, Cole CE, Tutsch K, et al. Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos [Ｊ]. Cancer Res, 2000; 60(7)∶1864.
  16. 16. 　吳高松, 劉正人, 鄒聲泉, 等. 塞來昔布(celecoxib)通過前列腺素E2途徑影響膽管癌細(xì)胞株生長和凋亡 [Ｊ]. 外科理論與實(shí)踐, 2003; 8(2)∶137.
  17. 17. 　Gately S. The contribution of cyclooxygenase-2 to tumor angiogenesis [Ｊ]. Cancer Metastasis Rev, 2001； 19(1－2)∶19.
  18. 18. 　Wu GS, Wang JH, Liu ZY, et al. Expression of cyclooxygenase-1 and -2 in extra-hepatic cholangiocarcinoma [Ｊ]. HBPD INT, 2002; 1(3)∶429.
  19. 19. 　Yao M, Kargman S, Lam EC, et al. Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice [Ｊ]. Cancer Res, 2003; 63(3)∶586.