戊烷硒啉与吉西他滨联合应用对胰腺癌的协同效应分析

doi:10.5246/jcps.2013.02.025

戊烷硒啉与吉西他滨联合应用对胰腺癌的协同效应分析

回艺, 马微微, 熊堃, 曾慧慧^*

北京大学医学部天然药物及仿生药物国家重点实验室, 北京 100191

收稿日期:2012-11-27 修回日期:2013-01-10 出版日期:2013-03-18 发布日期:2013-03-18
通讯作者: 曾慧慧*

Wbselen and gemcitabine synergistically inhibited the viability of JF305 and MiaPaCa-2 human pancreatic cancer cells

Yi Hui, Weiwei Ma, Kun Xiong, Huihui Zeng^*

State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China

Received:2012-11-27 Revised:2013-01-10 Online:2013-03-18 Published:2013-03-18
Contact: Huihui Zeng*

摘要/Abstract

摘要：

吉西他滨, 一种参与DNA合成和修复的细胞周期特异性抑制剂, 是目前胰腺癌化疗中唯一的一线药物, 但其单药化疗仅能将中位生存期延长5.65个月。因此, 临床胰腺癌的治疗仍需要开发新的药物和或联合方案。本次研究观察戊烷硒啉与吉西他滨联合应用体外抗人胰腺癌细胞的效应。MTT法检测戊烷硒啉与吉西他滨单药及不同联合方案对人胰腺癌细胞JF305和MiaPaCa-2的增殖抑制作用。采用Chou-Talalay的中位效应分析法计算不同联合给药方案的联合指数CI, 并比较单药与联合时所需吉西他滨剂量的变化。结果显示: 戊烷硒啉与吉西他滨联合可以减少吉西他滨起效时间, 降低IC50值和提高最大生长抑制率。在不同的联合给药方案中, 药物同时作用48小时后, 戊烷硒啉与吉西他滨比例为2:1和1:1时分别对JF305和MiaPaCa-2细胞显示出明显协同作用; 戊烷硒啉与吉西他滨联合作用两种细胞后, 随给药浓度的升高, 吉西他滨剂量明显减少, 尤以药物作用48小时突出。戊烷硒啉联合吉西他滨体外抗人胰腺癌细胞有协同增效作用。

关键词: 戊烷硒啉, 吉西他滨, 协同作用

Abstract:

Gemcitabine (GEM) is a cell-cycle specific inhibitor of DNA synthesis and repair, and has been applied as the first-line therapy for patients with locally advanced or metastatic pancreatic cancers. However, the median survival time is only 5.65 mon when GEM was administrated as a monothearpy. Therefore, novel therapeutic agents and/or combinations with GEM are needed for the treatment of pancreatic cancer. In this study, we aim to evaluate the efficacy of treatment with wbselen (WB), GEM, and combination treatment with GEM and WB in two pancreatic cancer cell lines, JF305 and MiaPaCa-2 cells. The combination index (CI) and the dose-reduction index (DRI) of combined treatment with different dose and time regimes were analyzed based on median-effect theory. Compared with single treatment with GEM, combination treatment displayed decreased response time and IC50, and increased maximum inhibition. Among the different combination regimes, the most significant synergistic effect was achieved when the dose ratios of WB to GEM was 2:1 in JF305 cells and 1:1 in MiaPaCa-2 cells after 48 h of drug treatment. When combinations of WB and GEM were used in these two cell lines, the dose of GEM was significantly reduced while the total drug concentration increased, especially after 48 h of drug treatments. Our results indicated that the combination treatment with WB and GEM had synergistic effect against pancreatic cancer in vitro.

Key words: Wbselen, Gemcitabine, Synergistic effect

中图分类号:

Supporting: ^*Corresponding author. Tel.: 86-10-82802878

回艺, 马微微, 熊堃, 曾慧慧^*. 戊烷硒啉与吉西他滨联合应用对胰腺癌的协同效应分析[J]. , DOI: 10.5246/jcps.2013.02.025.

Yi Hui, Weiwei Ma, Kun Xiong, Huihui Zeng^* . Wbselen and gemcitabine synergistically inhibited the viability of JF305 and MiaPaCa-2 human pancreatic cancer cells[J]. , DOI: 10.5246/jcps.2013.02.025.

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