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目的考察α-苦瓜素(α-MMC)对绒癌JAR细胞体外迁移侵袭行为的影响及其聚乙二醇(PEG)修饰物保留这一活性的程度。方法利用分子量为20 kDa的聚乙二醇氨基酸衍生物[(mPEG)2-Lys-NHS]以共价连接的方式对α-MMC分子表面进行修饰。采用MTT法、细胞黏附试验、划痕损伤试验、transwell法和明胶酶谱法分别检测JAR细胞经α-MMC或PEG-α-MMC作用后细胞的生长、存活、黏附、迁移、侵袭行为及分泌基质金属蛋白酶(MMPs)能力的变化。结果α-MMC及PEG-α-MMC依赖于剂量和时间方式显著抑制了绒癌JAR细胞的生长,PEG-α-MMC可保留67%天然α-MMC的抗增殖活性(1.5 mg.mL-1作用72 h)。经修饰后蛋白处理,细胞分泌的基质金属蛋白酶-2(MMPs-2)活性减弱,削弱了细胞的运动能力,JAR细胞的行进过程受到抑制。结论α-MMC及其PEG修饰物通过减弱MMPs-2活性抑制绒癌细胞的体外行进过程,首次揭示了核糖体失活蛋白可能影响体外肿瘤转移过程。
Objective To investigate the effect of α-MMC on the migration and invasion of choriocarcinoma JAR cells in vitro and the extent to which this modification is retained by polyethylene glycol (PEG) modifiers. Methods The molecular surface of α-MMC was modified by covalent attachment using polyethylene glycol amino acid derivative [(mPEG) 2-Lys-NHS] with a molecular weight of 20 kDa. The cell growth, survival, adhesion, migration, invasion and secretion of JAR cells were detected by MTT assay, cell adhesion assay, scratch injury assay, transwell assay and gelatin zymography respectively Changes in matrix metalloproteinases (MMPs) abilities. Results α-MMC and PEG-α-MMC significantly inhibited the growth of JAR cells in choriocarcinoma in a dosage and time-dependent manner. PEG-α-MMC retained the antiproliferative activity of 67% native α-MMC Effect 72 h). After modified protein treatment, the activity of MMPs-2 secreted by the cells weakened, impaired cell motility, and the progression of JAR cells was inhibited. Conclusion α-MMC and its PEG-modified compounds inhibit the in vitro process of choriocarcinoma cells by decreasing the activity of MMPs-2, revealing for the first time that ribosome-inactivating proteins may affect tumor metastasis in vitro.