Effects of Celecoxib on Proliferation of Human Colonic Cancer Cells and on The Hepatic Metastasis of Animal Model_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Wei ¹ , AN Jie ² , ZHANG Chao ¹ , LIU Zhankui. ¹

Department of General Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China;

Corresponding author：

Keywords：

Colonic neoplasm; Cyclooxygenase; Celecoxib

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Objective　 To evaluate the potential roles of celecoxib on proliferation and cell cycle progression of colon adenocarcinoma cells and on the hepatic metastasis of nude mice. Methods　The human colon cancer cells HT-29 and HCT-116 were employed in the study. After treatment with celecoxib, the inhibitory effects of celecoxib on the proliferation of cancer cells were quantified by MTT assay, and the cell cycle progression was detected by flow cytometry, tumor cells were inoculated in nude mice, and the hepatic metastasis was detected. Results　①Celecoxib inhibited the proliferation of the tumor cells in time and dose-dependent manners （P＜0.05，P＜0.01）. The inhibitory effect on HT-29 cells was ber than that on HCT-116 cells （P＜0.05）. ②Celecoxib changed cell cycle progression of both kinds of cells, and decreased the proliferation index of both kinds of cells too. ③Celecoxib could inhibit the growth of the hepatic metastatic tumor obviously. Conclusion　Celecoxib may inhibit the activity of cyclooxygenase-2, and resulting in the inhibition of division and proliferation, apoptosis of tumor cells and interfering in metastasis and relapse of colon cancer.

Citation： LIU Wei,AN Jie,ZHANG Chao,LIU Zhankui.. Effects of Celecoxib on Proliferation of Human Colonic Cancer Cells and on The Hepatic Metastasis of Animal Model. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2006, 13(6): 693-697. doi: Copy

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. 环氧化酶和非甾体类消炎药 [Ｊ]. 中国新药与临床杂志， 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.	吴高松, 刘正人, 邹声泉, 等. 塞来昔布(celecoxib)通过前列腺素E2途径影响胆管癌细胞株生长和凋亡 [Ｊ]. 外科理论与实践, 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. 　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. 环氧化酶和非甾体类消炎药 [Ｊ]. 中国新药与临床杂志， 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. 　吴高松, 刘正人, 邹声泉, 等. 塞来昔布(celecoxib)通过前列腺素E2途径影响胆管癌细胞株生长和凋亡 [Ｊ]. 外科理论与实践, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of Celecoxib on Proliferation of Human Colonic Cancer Cells and on The Hepatic Metastasis of Animal Model

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