在侵袭性前列腺癌细胞中,表型可塑性和对化疗剂的敏感性变化
Allan I Paxson1,2, Loren H Chang3, Jaime M C Gard2
1Partnership for Native American Cancer Prevention, University of Arizona, Tucson, AZ, United States.
侵袭性前列腺癌细胞对诸如沃里诺斯塔特等表观遗传抑制剂的敏感性增加,这表明了晚期疾病的新治疗标. 这一发现为更有效的前列腺癌治疗提供了希望.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 前列腺癌转移,是死亡的原因,涉及瘤的进展和外囊扩张.
- 隔离了一种具有攻击性,肌肉侵入性的前列腺癌细胞群体 (DU145J7),在表型,基因素H3K27水平和矩阵金属蛋白酶14表达方面与父DU145WT细胞不同.
研究的目的:
- 为了比较攻击性DU145J7前列腺癌细胞与非攻击性DU145WT细胞对各种化疗剂的敏感性.
主要方法:
- 对5578种瘤学化合物的高通量查.
- 11种化合物的选择和进一步测试.
- 使用IC50值来确定药物敏感性.
主要成果:
- 与DU145细胞相比,表观遗传抑制剂 (5-azacitidine,fimepinostat,vorinostat) 对DU145J7细胞的死亡率增加了2.6至7.5倍.
- DU145J7细胞对拓酶抑制剂 (mitoxantrone, daunorubicin, gimatecan) 的耐药性是2.2至4.0倍的.
- 在两种细胞群之间没有观察到对多塞塔克塞尔或皮拉鲁比辛的显著敏感性差异.
结论:
- 侵袭性,肌肉侵入性前列腺癌细胞 (DU145J7) 对染色素修饰剂的敏感性增加,表明潜在的治疗脆弱性.
- 未来的研究将专注于确定最佳的表观遗传修饰剂和组合,以根除早期侵袭性瘤种群.
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