Effect of celecoxib on the expression of NHE1 and intracellular pH in SGC-7901 gastric carcinoma cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SUN Dan , TAO Liping , LI Xiao , LU Jing , GENG Chong ,  WANG Chunhui

Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R.China;

Corresponding author：

WANG Chunhui, Email: wangch@scu.edu.cn

Keywords：

gastric carcinoma; celecoxib; sodium hydrogen exchanger 1; intracellular pH

DOI：

10.7507/1007-9424.201611052

Video：

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Objective To explore the effects of celecoxib, a selective COX-2 inhibitor, on the expression of NHE1 and intracellular pH (pHi) of SGC-7901 human gastric carcinoma cells. Methods Human gastric carcinoma cell line SGC-7901 was used as research object. MTT method was used to detect the celecoxib's depressant effect on the proliferation of SGC-7901 cells after intervening with different concentrations of celecoxib (5, 12.5, 25, 50, 75, and 100 μmol/L) for different time. Western blot was applied to detect influence of different concentrations of celecoxib on NHE1 expression in SGC-7901 human gastric carcinoma cells. On this basis, pHi of SGC-7901 cells was tested by BCECF-AM immunofluorescence. Results Celecoxib could effectively inhibit the proliferation of SGC-7901 human gastric carcinoma cells. And within a certain concentration range, the inhibitory action on SGC-7901 cells increased with the increase of celecoxib concentration. It also increased with the extension of explosion time while at the same concentration (P<0.05). Different concentrations (except 5 μmol/L) of celecoxib could down-regulate the expression of NHE1 in SGC-7901 cells, which was concentration dependent (P<0.05). The pHi of SGC-7901 cells that were not intervened with celecoxib is alkaline. Compared the pHi of cells in control group, the pHi of SGC-7901 cells decreased significantly after intervening with different concentrations of celecoxib (except 5 μmol/L) for 24 h (P<0.05). And the decrease of pHi was also concentration dependent (P<0.05). Conclusion Celecoxib may inhibit the growth of SGC-7901 cells through down-regulating the expression of NHE1 and declining the pHi.

Citation： SUN Dan, TAO Liping, LI Xiao, LU Jing, GENG Chong, WANG Chunhui. Effect of celecoxib on the expression of NHE1 and intracellular pH in SGC-7901 gastric carcinoma cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(4): 420-425. doi: 10.7507/1007-9424.201611052 Copy

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15.	Ouyang N, Williams JL, Rigas B. NO-donating aspirin inhibits angiogenesis by suppressing VEGF expression in HT-29 human colon cancer mouse xenografts. Carcinogenesis, 2008, 29(9): 1794-1798.
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20.	滕小春, 刘海峰. 人 NHE1 反义基因转染对 SGC-7901 胃癌细胞恶性表型的逆转作用. 现代肿瘤医学, 2006, 14(10): 1256-1259.
21.	Kaur J, Sanyal SN. Intracellular pH and calcium signaling as molecular targets of diclofenac-induced apoptosis against colon cancer. Eur J Cancer Prev, 2011, 20(4): 263-276.
22.	Kanwar SS, Roy KR, Nehru B,et al. Na⁺-stimulated Na⁺/H⁺ exchange and an unfavorable Ca²⁺ homeostasis initiate the cycloxygenase-2 inhibitors-induced apoptotic signals in colonic epithelial cells during the early stage of colon carcinogenesis. Oncol Res, 2009, 18(5): 243-257.
23.	Izumi H, Torigoe T, Ishiguchi H,et al. Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. Cancer Treat Rev, 2003, 29(6): 541-549.
24.	Lecureur V, Lagadic-Gossmann D, Fardel O. Potassium antimonyl tartrate induces reactive oxygen species-related apoptosis in human myeloid leukemic HL60 cells. Int J Oncol, 2002, 20(5): 1071-1076.
25.	Huc L, Sparfel L, Rissel M,et al. Identification of Na⁺/H⁺ exchange as a new target for toxic polycyclic aromatic hydrocarbons. FASEB J, 2004, 18(2): 344-346.

1. Parkin DM. International variation. Oncogene, 2004, 23(38): 6329-6340.
2. Sitarz R, Leguit RJ, de Leng WW,et al. Cyclooxygenase-2 mediated regulation of E-cadherin occurs in conventional but not early-onset gastric cancer cell lines. Cell Oncol, 2009, 31(6): 475-485.
3. Zhang LJ, Wang SY, Huo XH,et al. Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions. World J Gastroenterol, 2009, 15(22): 2731-2738.
4. Heming TA, Bidani A. Intracellular pH regulation in U937 human monocytes: roles of V-ATPase and Na/H exchange. Immunobiology, 2003, 207(2): 141-148.
5. Kim BM, Won J, Maeng KA,et al. Nimesulide, a selective COX-2 inhibitor, acts synergistically with ionizing radiation against A549 human lung cancer cells through the activation of caspase-8 and caspase-3. Int J Oncol, 2009, 34(5): 1467-1473.
6. Zhu FS, Chen XM, Huang ZG,et al. Rofecoxib augments anticancer effects by reversing intrinsic multidrug resistance gene expression in BGC-823 gastric cancer cells. J Dig Dis, 2010, 11(1): 34-42.
7. Ghosh N, Chaki R, Mandal V,et al. COX-2 as a target for cancer chemotherapy. Pharmacol Repr, 2010, 62(2): 233-244.
8. Méric JB, Rottey S, Olaussen K,et al. Cyclooxygenase-2 as a target for anticancer drug development. Crit Rev Oncol Hematol, 2006, 59(1): 51-64.
9. Dannenberg AJ, Altorki NK, Boyle JO,et al. Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol, 2001, 2(9): 544-551.
10. Dixon DA, Kaplan CD, McIntyre TM,et al. Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 3'-untranslated region. J Biol Chem, 2000, 275(16): 11750-11757.
11. Shao J, Sheng H, Inoue H,et al. Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells. J Biol Chem, 2000, 275(43): 33951-33956.
12. Yuan CJ, Mandal AK, Zhang Z,et al. Transcriptional regulation of cyclooxygenase-2 gene expression: novel effects of nonsteroidal anti-inflammatory drugs. Cancer Res, 2000, 60(4): 1084-1091.
13. 孙波, 吴云林, 张学军, 等. 舒林酸抑制人胃腺癌细胞增殖及诱导凋亡. 世界华人消化杂志, 2001, 9(9): 997-1002.
14. Uefuji K, Ichikura T, Shinomiya N,et al. Induction of apoptosis by JTE-522, a specific cyclooxygenase-2 inhibitor, in human gastric cancer cell lines. Anticancer Res, 2000, 20(6B): 4279-4284.
15. Ouyang N, Williams JL, Rigas B. NO-donating aspirin inhibits angiogenesis by suppressing VEGF expression in HT-29 human colon cancer mouse xenografts. Carcinogenesis, 2008, 29(9): 1794-1798.
16. Shtivelband MI, Juneja HS, Lee S,et al. Aspirin and salicylate inhibit colon cancer medium- and VEGF-induced endothelial tube formation: correlation with suppression of cyclooxygenase-2 expression. J Thromb Haemost, 2003, 1(10): 2225-2233.
17. Timoshenko AV, Chakraborty C, Wagner GF,et al. COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer. Br J Cancer, 2006, 94(8): 1154-1163.
18. Tahara T, Shibata T, Nakamura M,et al. Chronic aspirin use suppresses CDH1 methylation in human gastric mucosa. Dig Dis Sci, 2010, 55(1): 54-59.
19. Moody TW, Switzer C, Santana-Flores W,et al. Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells. Lung Cancer, 2010, 68(2): 154-160.
20. 滕小春, 刘海峰. 人 NHE1 反义基因转染对 SGC-7901 胃癌细胞恶性表型的逆转作用. 现代肿瘤医学, 2006, 14(10): 1256-1259.
21. Kaur J, Sanyal SN. Intracellular pH and calcium signaling as molecular targets of diclofenac-induced apoptosis against colon cancer. Eur J Cancer Prev, 2011, 20(4): 263-276.
22. Kanwar SS, Roy KR, Nehru B,et al. Na⁺-stimulated Na⁺/H⁺ exchange and an unfavorable Ca²⁺ homeostasis initiate the cycloxygenase-2 inhibitors-induced apoptotic signals in colonic epithelial cells during the early stage of colon carcinogenesis. Oncol Res, 2009, 18(5): 243-257.
23. Izumi H, Torigoe T, Ishiguchi H,et al. Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. Cancer Treat Rev, 2003, 29(6): 541-549.
24. Lecureur V, Lagadic-Gossmann D, Fardel O. Potassium antimonyl tartrate induces reactive oxygen species-related apoptosis in human myeloid leukemic HL60 cells. Int J Oncol, 2002, 20(5): 1071-1076.
25. Huc L, Sparfel L, Rissel M,et al. Identification of Na⁺/H⁺ exchange as a new target for toxic polycyclic aromatic hydrocarbons. FASEB J, 2004, 18(2): 344-346.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of celecoxib on the expression of NHE1 and intracellular pH in SGC-7901 gastric carcinoma cells

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