强力霉素抑制前列腺癌PC-3细胞的体外侵袭作用

MMPs inhibitor doxycycline suppresses invasion of PC-3 in vitro

目的 观察强力霉素 (Doxycycline)对恶性肿瘤细胞侵袭相关性质的影响 ,探讨金属蛋白酶抑制剂用于治疗肿瘤侵袭转移的可能性 .方法 PC 3细胞经 5mg·L-1,10mg·L-1和 2 0mg·L-1的强力霉素处理 2d后 ,分别用重建基底膜侵袭模型 ,粘附基质分析 ,Transwell小室趋化运动模型以及免疫组织化学分析和明胶酶谱分析来研究药物处理后PC 3细胞的侵袭性 ,粘附力及运动性和基质金属蛋白酶MMP 2表达和分泌的改变 .结果 经强力霉素处理后 ,PC 3细胞的侵袭能力明显减弱 ,趋化运动性降低 ,基质金属蛋白酶 (MMP 2 )的合成及分泌均受抑制 ,粘附率降低 ,且以上性质均具有剂量依赖性 .结论 强力霉素可以降低恶性肿瘤细胞的侵袭能力 ,改变侵袭相关性质 .金属蛋白酶抑制剂强力霉素有可能应用于肿瘤侵袭转移的治疗 .

AIM To investigate the effects of doxycycline, a matrix metalloproteinases (MMP) inhibitor, on the cancer invasion and associated cellular characteristics and to explore the possibility of developing MMP inhibitors as anti metastasis drugs. METHODS PC 3 cells were exposed to 5 mg·L -1 10 mg·L -1 and 20 mg·L -1 doxycycline conditional media for two days. The abilities of doxycycline treated cells to invade through reconsitituted matrigel or migrate through polycarbonate filters in transwell chambers were investigated. Immunohistochemistry and zymography analysis were performed to assess the expression and secretion of MMP 2 protein in cells treated with drug of different concentrations. RESULTS The ability of doxycycline treated cell to invade the reconstituted basement membrane was decreased significantly. In consistent with the lowered invasive potential, the migration rates of the drug treated cell decreased dramatically, Doxycycline also significantly affected the attachment of PC 3 cells on matrigel. Exposure to doxycycline led to a dramatic decrease in MMP 2 gene expression and MMP 2 secretion. CONCLUSION Doxycycline suppresses the invasion of PC 3 cells in a concentration dependence manner. Doxcycline and other MMP inhibitors are valuable candidate drugs for the treatment of invasion and metastasis of cancers.