中文摘要：

背景与目的：研究表明，肿瘤细胞MMP-2，MMP-9表达升高与其侵袭和转移能力有密切关系。因而，研究设计新的MMPs特异性抑制剂得到广泛重视。根据MMP-2，MMP-9结构特点，本实验设计合成全新结构的N1-取代咖啡酰吡咯烷类MMPs抑制剂——LY52，并观察该化合物对MMP-2，MMP-9表达的抑制作用及对人卵巢粘液囊腺上皮癌细胞SKOV3侵袭转移能力的影响。方法：MTT和细胞克隆法检测LY52对细胞生长抑制作用；明胶酶直接降解琥珀酰明胶法测定LY52抑酶作用活性：SDS-PAGE zymography分析对SKOV3细胞MMP-2，MMP-9表达的抑制作用；MTT法测定细胞与FN，LN和matfigel的粘附能力：Transwell小室法观察化合物对SKOV3细胞侵袭人工基底膜的抑制作用。结果：直接与细胞接触，LY52具有较弱的肿瘤细胞生长抑制作用。LY52直接抑制明胶酶活性，抑制作用IC50为11．9μg／ml。同时，LY52抑制SKOV3细胞MMP-2，MMP-9表达。以0．1、1、10、100、1000μg／ml剂量与SKOV3细胞孵育24h．对培养上清液MMP-2表达的抑制率为10．66％-31．47％：对MMP-9表达的抑制率为22．56％-56．71％。按上述剂量孵育1h。对SKOV3细胞与FN，LN和matfigel粘附能力的最大抑制率分别为29．79％，48．94％，50．92％。LY52显著抑制SKOV3细胞穿过人工基底膜能力，按上述剂量，LY52与细胞孵育24h，抑制率分别为7．5％，42．07％，66．54％，72．15％。82．84％。结论：LY52通过抑制SKOV3细胞MMP-2，MMP-9的表达．降低癌细胞侵袭转移能力。

英文摘要：

BACKGROUND ＆ OBJECTIVE. Enhanced expression and activation of matrix metalloproteinase-2 （MMP-2） and MMP-9 are associated with tumor progression, invasion, and metastasis. Using synthetic MMP inhibitors to block the proteolytic activity of these enzymes is a potential strategy of treating cancer. This study was to observe the inhibitory effects of LY52, a synthetic specific MMP inhibitor, on the expression of MMP-2 and MMP-9 and invasive ability of human ovarian carcinoma cell line SKOV3. METHODS： The inhibitory effect of LY52 on growth of SKOV3 cells was measured by MTT and clonogenic assays. The inhibitory effect of LY52 on the activity of gelatin was evaluated by spectrophotometry using succinylated gelatin as substrate. The inhibitory effect of LY52 on the expression of MMP-2 and MMP-9 was analyzed using SDS-PAGE zymography. The adhesive ability of SKOV3 cells to fibronectin （FN）, laminin （LN）, and matrigel was measured using MTT assay. The invasive ability of SKOV3 cells was assessed with a transwell cell culture chamber. RESULTS： LY52 had weak cytostatic effect on SKOV3 cells; the inhibitory rates were 10.54%-37.66% within 120 h incubation when the concentration was 10 μg/ml. LY52 inhibited gelatin degradation via suppressing the activities of gelatinases; the 50% inhibitory concentration （IC50） was 11.9μg/ml. When treated with 0.1, 1, 10, 100, or 1 000 μg/ml LY52 for 24 h, the expression of MMP-2 in SKOV3 cells was suppressed by 10.66%-31.47%, and the expression of MMP-9 was suppressed by 22.56%-56.71%. When treated with LY52 for 1 h, the maximum inhibitory rates of adhesion of SKOV3 cells to FN, LN, and matrigel were 29.79%, 48.94%, and 50.92%, respectively. When treated with 0.1, 1, 10, 100, and 1 000 μg/ml LY52 for 24 h, the inhibitory rates of invasion of SKOV3 cells were 7.5%, 42.07%, 66.54%, 72.15%, and 82.84%, respectively. CONCLUSION： LY52 suppresses the invasion of SKOV3 cells via inhibiting the expression of MMP-2 and MMP-9.