Qu Xianjun, Yuan Yunxia, Xu Wenfang, Chen Minghui, Cui Shuxiang, Meng Hong, Li Yan, Makuuchi Masatoshi, Nakata Munehiro, Tang Wei
School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Anticancer Res. 2006 Sep-Oct;26(5A):3573-8.
LY52 is a caffeoyl pyrrolidine derivative designed to fit and extend into the active pocket of matrix metalloproteinase (MMP). In this study, the effects of LY52 on MMP-2 and MMP-9 activities and tumor invasion and metastasis were examined.
MMP expression in SKOV3 cells was analyzed by gelatin zymography. The anti-invasion and anti-metastasis abilities of LY52 were evaluated with penetration of SKOV3 cells through Matrigel-coated membrane in vitro and pulmonary metastasis of Lewis lung carcinoma in mice, respectively.
LY52 significantly blocked the proteolytic activity of gelatinase. Gelatin zymography revealed that MMP-2 and MMP-9 expressions in SKOV3 cells were reduced in the presence of LY52. LY52 also suppressed SKOV3 cell invasion in vitro. Furthermore, a significant inhibition of pulmonary metastasis of Lewis lung carcinoma cells was observed in LY52-administrated mice.
LY52 might suppress invasion and metastasis of carcinoma cells via inhibition of MMP-2 and MMP-9 proteolytic activities.
LY52是一种咖啡酰吡咯烷衍生物，其设计目的是适配并延伸至基质金属蛋白酶（MMP）的活性口袋中。在本研究中，检测了LY52对MMP-2和MMP-9活性以及肿瘤侵袭和转移的影响。
通过明胶酶谱法分析SKOV3细胞中MMP的表达。分别利用SKOV3细胞穿透基质胶包被的膜的体外实验以及小鼠Lewis肺癌肺转移实验，评估LY52的抗侵袭和抗转移能力。
LY52显著阻断了明胶酶的蛋白水解活性。明胶酶谱法显示，在LY52存在的情况下，SKOV3细胞中MMP-2和MMP-9的表达降低。LY52还抑制了SKOV3细胞的体外侵袭。此外，在给予LY52的小鼠中观察到Lewis肺癌细胞肺转移受到显著抑制。
LY52可能通过抑制MMP-2和MMP-9的蛋白水解活性来抑制癌细胞的侵袭和转移。
