Abstract 978: Synergistic activity of EP-100 and chemotherapies in cancer cell lines.

长春瑞滨 紫杉醇 阿霉素 长春新碱 药理学 医学 联合化疗 癌症 顺铂 癌症研究 化疗 内科学 环磷酰胺
作者
Carola Leuschner,Shashi Gavini,Hector W. Alila
出处
期刊:Cancer Research [American Association for Cancer Research]
卷期号:73 (8_Supplement): 978-978 被引量:2
标识
DOI:10.1158/1538-7445.am2013-978
摘要

Abstract EP-100, a targeted anti-cancer drug comprised of a lytic peptide fused to Luteinizing Hormone Releasing Hormone (LHRH), is in Phase 2 clinical trial in tumors that over-express LHRH receptors in combination with paclitaxel. It kills cancer cells by membrane disruption. EP-100 was tested in combination with paclitaxel, vinorelbine, doxorubicin, cisplatinum, vincristine and 5 fluorouracil (5FU) in vitro. The sequence of adding EP-100 to the chemotherapeutics was tested in consideration of their half-lives (hours) than EP-100 (minutes). EP-100 was added to the cells before or after treatment with the chemotherapeutics to determine the order of treatment for maximum synergy. Cells were cultured in the presence of each single agent and in combination with EP-100 for 72h. Data were analyzed as IC50 values for each single drug and the combination with EP-100. Combination indices (CI) on interaction of EP-100 and each chemotherapeutic were determined. EP-100 alone was cytotoxic at low uM concentrations in LHRH receptor (+), multi-drug resistant human uterine sarcoma cell line MES-SA-Dx5 and a human breast cancer cell line MDA-MB-231 after 72 h incubation. Both cell lines were resistant to paclitaxel, vinorelbine, vincristine, 5-FU and cisplatinum. MES-SA-Dx5 cells were resistant to doxorubicin. Addition of EP-100 to each of the chemotherapeutics increased sensitivity to all of the drugs except 5-FU (Table 1). Combinations of EP-100 with paclitaxel, vincristine, vinorelbine, doxorubicin and cisplatinum resulted in potentiation of activity in a synergistic manner for both uterine sarcoma and breast cancer cell lines. The combination effects were synergistic with CIs of 0.2. The sequence of exposure was most potent when EP-100 was given first followed by incubation with paclitaxel, doxorubicin or vinorelbine. Table 1 In vitro activities (IC50 - nM) MES-SA-Dx5 Combination Index Potentiation MDA-MB-231 Combination Index Potentiation EP-100 Alone 3044 ± 558 1400 ± 300 Paclitaxel 33.7 ± 2.2 86.2 ± 5.9 EP100+Paclitaxel 0.014 ± 0.002 0.001 6000 15.9 ± 0.8 0.22 5.7 Vincristine 124.7 ± 16.3 26.3 ± 4.1 EP-100+Vincristine 5.7 ± 0.9 0.02 21.7 1.8 ± 0.1 0.09 15 Doxorubicin 32.6 ± 4.3 1.26 ± 0.4 EP-100+Doxorubicin 3.3 ± 0.6 0.09 9.6 1.1 ± 0.04 NA 1 Vinorelbine 63.22 ± 15.9 23.7 ± 3.4 EP-100+Vinorelbine 6.0 ± 1.6 0.06 10.5 3.1 ± 0.9 0.1 7.6 CDDP 54.5 ± 5.8 19.9 ± 6.2 EP-100 + CDDP 8.0 ± 2.6 0.2 6.8 8.1 ± 1.9 0.1 2.5 These results indicate that EP-100 synergizes with paclitaxel, doxorubicin, vinorelbine, vincristine and cisplatinum but not 5-FU in drug resistant human uterine sarcoma and breast cancer cells. Citation Format: Carola Leuschner, Shashi Gavini, Hector W. Alila. Synergistic activity of EP-100 and chemotherapies in cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 978. doi:10.1158/1538-7445.AM2013-978

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
renshiwufei发布了新的文献求助30
刚刚
刚刚
cenzy完成签到,获得积分10
刚刚
李健的小迷弟应助123采纳,获得20
1秒前
phoenix完成签到,获得积分0
1秒前
王淳完成签到,获得积分10
1秒前
还单身的薯片完成签到,获得积分10
1秒前
xinruru发布了新的文献求助10
1秒前
神勇的半莲完成签到,获得积分10
1秒前
2秒前
2秒前
起床了吗发布了新的文献求助50
2秒前
2秒前
在水一方应助小巧梦山采纳,获得10
2秒前
林渊发布了新的文献求助10
3秒前
勾勾1991完成签到,获得积分10
3秒前
Echoheart完成签到,获得积分10
4秒前
青城完成签到,获得积分10
4秒前
TianFuAI发布了新的文献求助10
4秒前
Ding应助小杨采纳,获得10
4秒前
shinysparrow应助Rainielove0215采纳,获得200
5秒前
smottom应助机灵的觅露采纳,获得10
6秒前
6秒前
ccc发布了新的文献求助10
7秒前
果果发布了新的文献求助20
7秒前
搬砖人完成签到,获得积分10
7秒前
桐桐应助王淳采纳,获得10
8秒前
李星发布了新的文献求助10
8秒前
Lmding完成签到,获得积分10
8秒前
hhhhhh应助amigo采纳,获得10
8秒前
eno完成签到,获得积分10
8秒前
高等游民完成签到,获得积分10
8秒前
情怀应助陈陈采纳,获得10
8秒前
chen完成签到,获得积分10
8秒前
8秒前
子里完成签到,获得积分10
9秒前
林小雨完成签到,获得积分10
9秒前
10秒前
whale发布了新的文献求助10
10秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Social Research Methods (4th Edition) by Maggie Walter (2019) 2390
A new approach to the extrapolation of accelerated life test data 1000
北师大毕业论文 基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 390
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
Robot-supported joining of reinforcement textiles with one-sided sewing heads 360
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4009254
求助须知:如何正确求助?哪些是违规求助? 3549107
关于积分的说明 11300780
捐赠科研通 3283530
什么是DOI,文献DOI怎么找? 1810370
邀请新用户注册赠送积分活动 886168
科研通“疑难数据库(出版商)”最低求助积分说明 811267