転移抑制剤としての抗癌剤の作用機序:抗癌剤による卵巣癌のmatrix metalloproteinases(MMPs)発現制御をモデルとして

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In order to understand the ability of human ovarian cancers to degrade the extra-cellular matrix, we studied the expression of matrix metalloproteinases (MMPs) 1,2,3 and 9 and their tissue inhibitors (TIMPs) 1 and 2 in a panel of human ovarian cancer cell lines. Their regulation after the treatment with anti-cancer agents (CDDP, paclitaxel, etoposide, CPM or doxorubicin) was also investigated. In Western, Southern and Northern analysis using monoconal antibodies to MMPs or TIMPs and their cDNA probes, the frequency of MMP-1,2 and 9 expression was 67%,17% and 67%. None produced MMP-3. TIMP-1 was undetectable in 50% of cell lines, but TIMP-2 was expressed in the majority. As for MMP-1, effective ratios (inhibition concentration (IC) of cytotoxicity / IC of MMP-1 expression) of CDDP and paclitaxel were much larger than other agents, suggesting their potential ability of anti-metastatic action. Nevertheless, MMP-1 expression was significantly up-regulated (up to 30%) in the lower concentrations of CDDP treatment ranging from O.5to 1.0μ9/ml, which suggests the ability of CDDP to promote the invasive potential of ovarian cancer cells in specific conditions.
Kinki Brain Tumor Pathology Conferenceの論文