Abstract
Matrix metalloproteinase 7 (MMP7) was reported to be a negative regulator in Fas-mediated apoptosis. The mechanism of cell killing associated with 5-FU treatment in colon cancer was also closely related to Fas-induced apoptosis, which implied that the expression level of MMP7 in colorectal cancer may be associated with the sensitivity of 5-FU treatment. To prove the hypothesis, first we verified the negative relevance between the colorectal cancer cells apoptosis in response to 5-FU treatment and MMP7 level by MTT and flow cytometry assay in vitro. Further, we found the apoptosis was in a positive relation with the Fas ligand level collected from the medium, suggesting a Fas-induced apoptosis. We found that increased level of MMP7 resulted in the enhanced drug resistance in SW620 colon cancer cells treated with 5-FU in vitro. Besides, we analyzed the influence of MMP7 on prognosis of 76 patients with TNM stage II-III colorectal cancers who had undergone curative resections and received 5-FU-based adjuvant chemotherapy. The expression of MMP7 was detected by IHC, and the relationship between the expression of MMP7 and disease-free survival was analyzed by univariate analysis and multivariate analysis. Patients with higher expression of MMP7 showed inferior disease-free survival (p=0.007), and high expression of MMP7 was a significant independent unfavorable prognostic factor (p=0.012). These data suggested that MMP7 is a useful marker for 5-FU chemotherapy sensitivity in patients with stage II-III colorectal cancer.