[4-acetamidophenyl retinoate (4-APR) inhibits reconstituted basement membrane invasion by tumor cells and its mechanism]

Abstract

Objective: To study the inhibitory effect of new retinoid 4-acetamidophenyl retinoate (4-APR) on the reconstituted basement membrane invasion by B16-F10 mouse melanoma cells and its mechanism.

Methods: Reconstituted basement membrane invasion assay was used to evaluate invasive ability of cancer cells. Type IV collagenase was assessed by PAGE substrate zymography. TIMP-1 mRNA expression of human nasopharyngeal carcinoma CNE-2Z cell line was measured by dot blot analysis. Cell growth curve assay was used to examine the growth inhibitory effect of 4-APR on B16-F10 cells.

Results: 4-APR, at the concentrations of 10(-5) mol/L and 10(-6) mol/L, suppressed the reconstituted basement membrane invasion of B16-F10 mouse melanoma cells by 54.2%, 41.9% and reduced type IV collagenase activities in the serum-free supernatant of CNE-2Z cells. In addition, 4-APR inhibited B16-F10 cell adherence to laminin, fibronectin and Matrigel, and induced CNE-2Z cell TIMP-1 mRNA expression.

Conclusion: Reconstituted basement membrane invasion of B16-F10 mouse melanoma cells was inhibited by 4-APR. The anti-invasion action of 4-APR might be associated with the suppression of tumor cell adhesion ability, the reduction of type IV collagenase activity in tumor cell culture supernatant and/or the induction of tumor cell TIMP-1 mRNA expression.