Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase‑2 expression

Sun,Kun; Tang,Xiao‑He; Xie,Yi‑Kui

doi:10.3892/ol.2015.3425

Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase‑2 expression

Authors:
- Kun Sun
- Xiao‑He Tang
- Yi‑Kui Xie
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Affiliations: Department of Gastroenterology, The First Hospital of Zibo, Zibo, Shandong 255200, P.R. China
Published online on: June 25, 2015 https://doi.org/10.3892/ol.2015.3425
Pages: 1649-1654

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Abstract

Cyclooxygenase‑2 (COX‑2) has a critical role in the invasiveness and metastasis of gastric cancer. In addition, paclitaxel (PTX) and harmine (HM) were reported to be potential therapeutic drug candidates for cancer therapy; however, the synergistic antitumor effect of PTX and HM combined treatment on the human gastric cancer cells remains to be elucidated. The aim of the present study was to evaluate the effects of PTX and/or HM on the cell migration and invasion in two human gastric cancer cell lines, SGC‑7901 and MKN‑45. MTT assay was used to detect the growth inhibition induced by PTX and HM . The Transwell assay was employed to assess the effects of PTX and HM on the cell migration and invasion. The expression levels of COX-2 and matrix metalloproteinase-9 (MMP-9) were analyzed by western blot analysis. The results demonstrated that PTX and HM inhibited cell proliferation in a dose‑dependent manner. Individually PTX and HM were able to inhibit the migration and invasion of two human gastric cancer cells; however, the combination of PTX and HM exerted synergistic effects on migration and invasion inhibition, with downregulation of COX‑2 and matrix metalloproteinase (MMP)‑9. In conclusion, the results of the present study indicated that combination chemotherapy using PTX with HM exerted an antitumor effect, which may be implicated for the treatment of gastric cancer. Of note, the combination of the two drugs inhibited migration and invasion more effectively compared with each drug alone, the mechanism of which proceeded via the downregulation of COX‑2 expression.

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1	Smith MG, Hold GL, Tahara E and El-Omar EM: Cellular and molecular aspects of gastric cancer. World J Gastroenterol. 12:2979–2990. 2006.PubMed/NCBI
2	Lee JH, Kim KM, Cheong JH and Noh SH: Current management and future strategies of gastric cancer. Yonsei Med J. 53:248–257. 2012. View Article : Google Scholar : PubMed/NCBI
3	Sakamoto J, Matsui T and Kodera Y: Paclitaxel chemotherapy for the treatment of gastric cancer. Gastric Cancer. 12:69–78. 2009. View Article : Google Scholar : PubMed/NCBI
4	Cao MR, Li Q, Liu ZL, Liu HH, Wang W, Liao XL, Pan YL and Jiang JW: Harmine induces apoptosis in HepG2 cells via mitochondrial signaling pathway. Hepatobiliary Pancreat Dis Int. 10:599–604. 2011. View Article : Google Scholar : PubMed/NCBI
5	Liao X, Che X, Zhao W, Zhang D, Bi T and Wang G: The β -adrenoceptor antagonist, propranolol, induces human gastric cancer cell apoptosis and cell cycle arrest via inhibiting nuclear factor κB signaling. Oncol Rep. 24:1669–1676. 2010.PubMed/NCBI
6	Zhang H, Sun K, Ding J, Xu H, Zhu L, Zhang K, Li X and Sun W: Harmine induces apoptosis and inhibits tumor cell proliferation, migration and invasion through down-regulation of cyclooxygenase-2 expression in gastric cancer. Phytomedicine. 21:348–355. 2014. View Article : Google Scholar : PubMed/NCBI
7	Sun WH, Sun YL, Fang RN, Shao Y, Xu HC, Xue QP, Ding GX and Cheng YL: Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis. Jpn J Clin Oncol. 35:707–713. 2005. View Article : Google Scholar : PubMed/NCBI
8	Huang F, Lin C, Shi YH and Kuerban G: MicroRNA-101 inhibits cell proliferation, invasion, and promotes apoptosis by regulating cyclooxygenase-2 in Hela cervical carcinoma cells. Asian Pac J Cancer Prev. 14:5915–5920. 2013. View Article : Google Scholar : PubMed/NCBI
9	Chan MW, Wong CY, Cheng AS, Chan VY, Chan KK, To KF, Chan FK, Sung JJ and Leung WK: Targeted inhibition of COX-2 expression by RNA interference suppresses tumor growth and potentiates chemosensitivity to cisplatin in human gastric cancer cells. Oncol Rep. 18:1557–1562. 2007.PubMed/NCBI
10	Sun WH, Zhu F, Chen GS, Su H, Luo C, Zhao QS, Zhang Y, Shao Y, Sun J, Zhou SM, et al: Blockade of cholecystokinin-2 receptor and cyclooxygenase-2 synergistically induces cell apoptosis, and inhibits the proliferation of human gastric cancer cells in vitro. Cancer Lett. 263:302–311. 2008. View Article : Google Scholar : PubMed/NCBI
11	Ram M, Sherer Y and Shoenfeld Y: Matrix metalloproteinase-9 and autoimmune diseases. J Clin Immunol. 26:299–307. 2006. View Article : Google Scholar : PubMed/NCBI
12	Velinov N, Poptodorov G, Gabrovski N and Gabrovski S: The role of matrixmetalloproteinases in the tumor growth and metastasis. Khirurgiia (Sofiia). 1:44–49. 2010.(In Bulgarian). PubMed/NCBI
13	He XP, Shao Y, Li XL, Xu W, Chen GS, Sun HH, Xu HC, Xu X, Tang D, Zheng XF, et al: Downregulation of miR-101 in gastric cancer correlates with cyclooxygenase-2 overexpression and tumor growth. FEBS J. 279:4201–4212. 2012. View Article : Google Scholar : PubMed/NCBI
14	Liu W, Yang Q, Liu B and Zhu Z: Serum proteomics for gastric cancer. Clin Chim Acta. 431:179–184. 2014. View Article : Google Scholar : PubMed/NCBI
15	Neugut AI, Hayek M and Howe G: Epidemiology of gastric cancer. Semin Oncol. 23:281–291. 1996.PubMed/NCBI
16	Tuan TF, Tsai ML, Yeh KC, Huang HC, Chung CT, Huang CL, Han CH, Chen CP, Wang MH, Shen CC, et al: Intravenous paclitaxel against metastasis of human gastric tumors of diffuse type. Cancer Chemother Pharmacol. 66:773–783. 2010. View Article : Google Scholar : PubMed/NCBI
17	Papadaki C, Mavroudis D, Trypaki M, Koutsopoulos A, Stathopoulos E, Hatzidaki D, Tsakalaki E, Georgoulias V and Souglakos J: Tumoral expression of TXR1 and TSP1 predicts overall survival of patients with lung adenocarcinoma treated with first-line docetaxel-gemcitabine regimen. Clin Cancer Res. 15:3827–3833. 2009. View Article : Google Scholar : PubMed/NCBI
18	Williams CS, Smalley W and DuBois RN: Aspirin use and potential mechanisms for colorectal cancer prevention. J Clin Invest. 100:1325–1329. 1997. View Article : Google Scholar : PubMed/NCBI
19	O'Mahony CA, Beauchamp RD, Albo D, Tsujii M, Sheng HM, Shao J, Dubois RN and Berger DH: Cyclooxygenase-2 alters transforming growth factor-beta 1 response during intestinal tumorigenesis. Surgery. 126:364–370. 1999. View Article : Google Scholar : PubMed/NCBI
20	Liu XH, Kirschenbaum A, Yao S, Stearns ME, Holland JF, Claffey K and Levine AC: Upregulation of vascular endothelial growth factor by cobalt chloride-simulated hypoxia is mediated by persistent induction of cyclooxygenase-2 in a metastatic human prostate cancer cell line. Clin Exp Metastasis. 17:687–694. 1999. View Article : Google Scholar : PubMed/NCBI