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World J Gastroenterol. Jul 14, 2008; 14(26): 4227-4233
Published online Jul 14, 2008. doi: 10.3748/wjg.14.4227
Mechanisms underlying aspirin-mediated growth inhibition and apoptosis induction of cyclooxygenase-2 negative colon cancer cell line SW480
Ming-Yu Lai, Jie-An Huang, Zhi-Hai Liang, Hai-Xing Jiang, Guo-Du Tang
Ming-Yu Lai, Jie-An Huang, Zhi-Hai Liang, Hai-Xing Jiang, Guo-Du Tang, Department of Gastroenterology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Author contributions: Lai MY and Huang JA designed the research; Lai MY, Liang ZH and Jiang HX performed the research; Huang JA contributed to the new reagents/analytic tools; Liang ZH and Jiang HX analyzed the data; Lai MY and Tang GD wrote the paper.
Correspondence to: Jie-An Huang, MD, PhD, Department of Gastroenterology, First Affiliated Hospital, Guangxi Medical University, No. 6 Shuangyong Rd, Nanning 530021, Guangxi Zhuang Autonomous Region, China. jhuangnews@hotmail.com
Telephone: +86-771-5356501
Fax: +86-771-5351574
Received: April 16, 2008
Revised: June 17, 2008
Accepted: June 24, 2008
Published online: July 14, 2008
Abstract

AIM: To investigate the effects of aspirin (acetylsalicylic acid) on proliferation and apoptosis of colorectal cancer cell line SW480 and its mechanism.

METHODS: Cyclooxygenase (COX)-2 negative colorectal cancer cell line SW480 was treated with aspirin at concentrations of 2.5 mmol/L, 5.0 mmol/L, 10.0 mmol/L for different periods in vitro. Anti-proliferation effect of aspirin on SW480 was detected by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and apoptosis were observed by flow cytometry (FCM). Transmission electron microscope (TEM) was used for morphological study. Apoptosis-associated genes were detected by immunohistochemical staining and Western blotting.

RESULTS: Aspirin inhibited SW480 proliferation and induced apoptosis in a dose- and time-dependent manner. Treatment with different concentrations of aspirin significantly increased the proportions of cells at the G0/G1 phase and decreased the proportions of cells at the S- and G2/M phases in a concentration-dependent manner. Aspirin not only induced apoptosis but also caused cell necrosis at a high concentration as well. After treatment with aspirin, SW480 cells displayed typically morphological features of apoptosis and necrosis under TEM, and increased the Bcl-2 expression in cells, but the expression of Bax was down regulated.

CONCLUSION: Aspirin inhibits proliferation and induces apoptosis of SW480 cells. Its anti-tumor mechanism may arrest cell cycle and shift Bax/Bcl-2 balance in cells.

Keywords: Aspirin; Colorectal cancer; Proliferation; Apoptosis