首页> 美国卫生研究院文献>other >Farnesyltransferase inhibitor R115777 inhibits cell growth and induces apoptosis in mantle cell lymphoma
【2h】

Farnesyltransferase inhibitor R115777 inhibits cell growth and induces apoptosis in mantle cell lymphoma

机译:法尼基转移酶抑制剂R115777抑制细胞生长并诱导套细胞淋巴瘤凋亡

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

The cytotoxic activity of the farnesyltranseferase inhibitor R115777 was evaluated in cell lines representative of mantle cell lymphoma (MCL). Cell growth, proliferation, and apoptosis were analyzed in four human MCL cell lines (Granta, NCEB, REC, and UPN1) in presence of R115777, alone or in combination with vincristin, doxorubicin, bortezomib, cisplatin and cytarabine. Inhibition of farnesylation was determined by the appearance of prelamin A. The antitumor activity of R115777, administered p.o. at 100, 250 and 500mg/kg, was determined in vivo in nude mice xenografted with UPN1 cells. R115777 inhibited the growth of MCL cell lines in vitro with inhibitory concentrations ranging between 2 and 15nM. A fifty percent decrease of cell viability was observed at concentrations comprised between 0.08 and 17μM. Apoptosis, evaluated by annexin V and activated caspase 3 staining, was induced in all cell lines, in 40 to 71% of the cells depending on the cell lines. In addition, R115777 significantly increased the cytotoxic effect of vincristine, doxorubicin, bortezomib, cisplatin and cytarabine (p=0.001, p=0.016, p=0.006, p=0.014 and p=0.007 respectively). Exposure of MCL cell lines to R115777 during 72 hours resulted in inhibition of protein farnesylation. R115777 administered p.o. twice daily for 8 consecutive days to mice bearing established s.c. UPN1 xenograft displayed cytostatic activity at the 500 mg/kg dosage. We have demonstrated that inhibition of farnesyltransferase by R115777 was associated with growth inhibition and apoptosis of MCL cell lines in vitro and tumor xenograft stability in vivo.
机译:在代表套细胞淋巴瘤(MCL)的细胞系中评估了法呢基转铁酶抑制剂R115777的细胞毒活性。在存在R115777的四种人类MCL细胞系(Granta,NCEB,REC和UPN1)中,单独或与长春新碱,阿霉素,硼替佐米,顺铂和阿糖胞苷组合,分析了细胞的生长,增殖和凋亡。法尼基化的抑制作用是通过prelamin A的出现来确定的。p115给予R115777的抗肿瘤活性。在用UPN1细胞异种移植的裸鼠体内测定了100、250和500mg / kg的浓度。 R115777在体外抑制MCL细胞系的生长,抑制浓度范围为2到15nM。在0.08至17μM之间的浓度下观察到细胞活力降低了百分之五十。通过膜联蛋白V和活化的胱天蛋白酶3染色评估的凋亡在所有细胞系中被诱导,取决于细胞系在40至71%的细胞中被诱导。此外,R115777显着提高了长春新碱,阿霉素,硼替佐米,顺铂和阿糖胞苷的细胞毒性作用(分别为p = 0.001,p = 0.016,p = 0.006,p = 0.014和p = 0.007)。在72小时内将MCL细胞系暴露于R115777会导致蛋白法尼基化的抑制。 R115777口服每天两次两次,连续8天给已建立s.c.的小鼠。 UPN1异种移植物在500 mg / kg剂量下显示出细胞抑制活性。我们已经证明,R115777对法呢基转移酶的抑制作用与体外MCL细胞系的生长抑制和凋亡以及体内肿瘤异种移植物的稳定性有关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号