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


CONCLUSIONS
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.
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
B
B
Shi
R
R
Han
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001485:Basement Membrane / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D017364:Collagenases / Q000378:metabolism; D006801:Humans; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D012176:Retinoids / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
C413931:4-acetamidophenyl retinoate; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D012176:Retinoids; D019715:Tissue Inhibitor of Metalloproteinase-1; D017364:Collagenases