Acetylsalicylic acid regulates MMP-2 activity and inhibits colorectal invasion of murine B16F0 melanoma cells in C57BL/6J mice: effects of prostaglandin F(2)alpha.
Epidemiological studies indicate that acetylsalicylic acid may reduce the risk of mortality due to colon cancers. Metastasis is the major cause of cancer death. Matrix metalloproteinases (MMPs) play important roles in tumor invasion regulation, and prostaglandin F(2)alpha (PGF(2)alpha) is a key stimulator of MMP production. Thus, we investigated whether acetylsalicylic acid regulated MMP activity and the invasion of cancer cells and whether PGF(2)alpha attenuated acetylsalicylic acid-inhibited invasion of cancer cells. Gelatin-based zymography assays showed that acetylsalicylic acid inhibited the MMP-2 activity of B16F0 melanoma cells. Matrigel-based chemoinvasion assays showed that acetylsalicylic acid inhibited the invasion of B16F0 cells. Acetylsalicylic acid can inhibit PGF(2)alpha synthesis and PGF(2)alpha is a key stimulator of MMP-2 production. Our data showed that PGF(2)alpha treatment attenuated the acetylsalicylic acid-inhibited invasion of B16F0 cells. In animal experiments, acetylsalicylic acid reduced colorectal metastasis of B16F0 cells in C57BL/6J mice by 44%. Our results suggest that PGF(2)alpha is a therapeutic target for metastasis inhibition and acetylsalicylic acid may possess anti-metastasis ability.
Tsai
Chin-Shaw Stella
CS
Department of Otolaryngology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
Luo
Shue-Fen
SF
Ning
Chung-Chu
CC
Lin
Chien-Liang
CL
Jiang
Ming-Chung
MC
Liao
Ching-Fong
CF
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000556:secondary*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015237:Dinoprost / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness
D016588:Anticarcinogenic Agents; D016861:Cyclooxygenase Inhibitors; D015237:Dinoprost; D020778:Matrix Metalloproteinase 2; D001241:Aspirin