4—乙酰胺苯基维甲酸酯抑制肿瘤细胞侵袭重组基底膜及其作用机理

目的研究新维甲类化合物４－乙酰胺苯基维甲酸酯（４－ＡＰＲ）对Ｂ１６－Ｆ１０小鼠黑色素瘤细胞侵袭能力的抑制作用,探讨其作用机理。方法癌细胞侵袭能力用重组基底膜侵袭试验衡量;ＰＡＧＥ底物酶谱方法检测Ⅳ型胶原酶活性;斑点杂交检测ＣＮＥ－２Ｚ细胞ＴＩＭＰ－１ｍＲＮＡ表达;以细胞生长曲线评价药物对Ｂ１６－Ｆ１０细胞的生长抑制作用。结果在１０－５ｍｏｌ／Ｌ和１０－６ｍｏｌ／Ｌ时,４－ＡＰＲ对Ｂ１６－Ｆ１０小鼠黑色素瘤细胞侵袭重组基底膜的抑制率分别为５４．２％和４１．９％,对ＣＮＥ－２Ｚ细胞培养上清中的Ⅳ型胶原酶活性有降低作用。此外,４－ＡＰＲ可抑制Ｂ１６－Ｆ１０细胞与ＬＮ、ＦＮ和Ｍａｔｒｉｇｅｌ的粘附,诱导ＣＮＥ－２Ｚ细胞ＴＩＭＰ－１ｍＲＮＡ表达。结论４－ＡＰＲ抑制Ｂ１６－Ｆ１０细胞侵袭重组基底膜。４－ＡＰＲ的抗侵袭活性与抑制肿瘤细胞的粘附,降低肿瘤细胞培养上清中Ⅳ型胶原酶的活性和（或）诱导肿瘤细胞ＴＩＭＰ－１ｍＲＮＡ表达等有关。

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. 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.