【摘要】 目的 观察genistein对恶性肿瘤细胞侵袭及侵袭相关性质的影响，探讨蛋白酪氨酸激酶抑制剂用于肿瘤转移治疗的可能性。方法 HT1080细胞经20μmol/L或40 μmol/L Genistein处理3天后，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Northernblot分析来研究药物处理后细胞侵袭、粘附、运动以及基质蛋白酶基因表达的改变。结果 经genistein处理后，HT1080细胞的侵袭能力明显下降,趋化运动能力降低,基质金属蛋白酶抑制剂(TIMP-1)基因相对表达量增加，但粘附率没有降低。结论 genistein可降低恶性肿瘤细胞的侵袭能力,改变侵袭相关性质。

Protein tyrosine kinaseinhibitor genistein suppresses in vitro invasion of HT1080 human fibrosarcoma cells

YAN Chunhong, HAN Rui.

    Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050

【Abstract】 Objective Toinvestigate the effects of genistein on cancer invasion and associated cellularcharacteristics and explore the possibility of developing protein tyrosine kinaseinhibitors as anti-metastasis drugs. Methods HT1080 human fibrosarcomacells were exposed to 20 μmol/L or 40 μmol/L genistein for 3 days. The abilities of the genistein-treated cells to invade through reconstituted matrigel or migrate throughpolycarbonate filters in transwell chambers were then investigated. Northern blot andlaser densitometry were used to estimate the relative mRNA amounts of MMP-2, MMP-9 andTIMP-1 in the cells. Results The ability of the genistein-treatedHT1080 cells to invade the reconstituted basement membrane was decreased significantly(P<0.01). In consistent with the lowered invasive potential, migration rates of thedrug-treated cells decreased dramatically. genistein did not, however, significantlyaffect attachment of HT1080 cells on fibronectin, laminin or Matrigel. Though exposure togenistein led to a small increase in MMP-2 and MMP-9 gene expression, a much greaterincrease in the amount of TIMP-1 mRNA was observed. Imbalanced enhancement of geneexpression between matrix metalloproteinases and their inhibitors in favor of the lattermay imply that matrix degradation is impaired in the genistein-treated cells. Conclusion genisteinsuppresses invasion of HT1080 cells at relatively low concentrations. genistein and otherprotein tyrosine kinase inhibitors might be valuable candidate drugs for the treatment ofinvasion and metastasis of cancer.

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