Mechanisms underlying aspirin-mediated growth inhibition and apoptosis induction of cyclooxygenase-2 negative colon cancer cell line SW480.
OBJECTIVE
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-dimethylthiazol-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 G(0)/G(1)phase and decreased the proportions of cells at the S- and G(2)/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.


CONCLUSIONS
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.
Lai
Ming-Yu
MY
Department of Gastroenterology, First Affiliated Hospital, Guangxi Medical University, No. 6 Shuangyong Rd, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
Huang
Jie-An
JA
Liang
Zhi-Hai
ZH
Jiang
Hai-Xing
HX
Tang
Guo-Du
GD
D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000032:analysis*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000032:analysis
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D001241:Aspirin