CLA-PTX对黑色素瘤B16-F10的体内外抗肿瘤作用

doi:10.5246/jcps.2014.01.007

中国药学(英文版) ›› 2014, Vol. 23 ›› Issue (1): 46-53.DOI: 10.5246/jcps.2014.01.007

CLA-PTX对黑色素瘤B16-F10的体内外抗肿瘤作用

李捷思, 杨科, 柯曦宇, 杜若, 张烜^*, 张强

1. 北京大学医学部药学院药剂学系, 北京 100191
2. 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:2013-03-26 修回日期:2013-05-07 出版日期:2014-01-23 发布日期:2014-01-22
通讯作者: 张烜*
作者简介:*Corresponding author. Tel./Fax: +86-10-82802683; E-mail: xuanzhang@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81172992) and the National Basic Research Program of China (973 Program, Grant No. 2009CB930300) and Innovation Team of Ministry of Education (Grant No. BMU20110263).

In vitro and in vivo antitumor efficacy of CLA-PTX on B16-F10 melanoma cells

Jiesi Li, KeYang, Xiyu Ke, Ruo Du, Xuan Zhang^*, Qiang Zhang

1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2013-03-26 Revised:2013-05-07 Online:2014-01-23 Published:2014-01-22
Contact: Xuan Zhang*
About author:*Corresponding author. Tel./Fax: +86-10-82802683; E-mail: xuanzhang@bjmu.edu.cn
Supported by:
National Natural Science Foundation of China (Grant No. 81172992) and the National Basic Research Program of China (973 Program, Grant No. 2009CB930300) and Innovation Team of Ministry of Education (Grant No. BMU20110263).

摘要/Abstract

摘要：

本研究旨在探索CLA-PTX对黑色素瘤B16-F10细胞的体内外抗肿瘤作用。选择鼠源B16-F10细胞系作为研究模型。研究CLA-PTX体外细胞毒, 细胞凋亡, 细胞周期作用, 以及CLA-PTX体外细胞摄取作用。用荷瘤C57BL6/N小鼠研究CLA-PTX的体内抗肿瘤作用。体外细胞毒研究结果表明: CLA-PTX的IC₅₀为(4.25±0.43) µM, 优于紫杉醇(6.70±0.80) µM (P<0.01)。与空白组和紫杉醇组相比, CLA-PTX可使细胞总凋亡比例增加(P<0.01)。与空白对照组相比, CLA-PTX将细胞周期阻滞于S期, 而紫杉醇则使细胞在G₂-M期蓄积。CLA-PTX的细胞摄取量显著高于紫杉醇(P<0.01)。体内抗肿瘤药效显示, CLA-PTX抗肿瘤活性显著高于空白对照组和紫杉醇组(P<0.01或P<0.05)。上述结果表明, CLA-PTX对B16-F10细胞有显著体内外抗肿瘤作用。

关键词: CLA-PTX, 凋亡, 细胞周期, 细胞摄取, 抗肿瘤作用

Abstract:

The purpose of this study was to investigate the potential antitumor efficacy of conjugated linoleic acid-paclitaxel (CLA-PTX) on B16-F10 melanoma cell line in vitro and in vivo. The in vitro cytotoxicity, apoptosis and cell cycle of CLA-PTX were investigated. The in vitro cellular uptake of CLA-PTX in B16-F10 cells was also analyzed. The antitumor activity of CLA-PTX was also evaluated in B16-F10 tumor-bearing C57BL6/N mice in vivo. The in vitro cytotoxicity results showed that the IC₅₀ of the CLA-PTX is (4.25±0.43) µM, compared with that of (6.70±0.80) µM in PTX treatment group (P<0.01). CLA-PTX increased the percentage of total apoptotic cells compared with that of control and PTX treatment groups (P<0.01). Compared with untreated cells, CLA-PTX arrested cell cycle progression at the S phase, whereas PTX caused accumulation of cell at G₂-M phase both along with the reduction of the cellular fraction arrested at the G₁ phase. The amount of cellular uptake of CLA-PTX was significantly higher than that of PTX (P<0.01). The in vivo antitumor activity of CLA-PTX was significantly higher than that of control and PTX treatment groups (P<0.01 or P<0.05). In conclusion, our study demonstrated that CLA-PTX has significant antitumor activity in B16-F10 cell line.

Key words: CLA-PTX, Apoptosis, Cell cycle, Cellular uptake, Antitumor efficacy

中图分类号:

R943

Supporting: National Natural Science Foundation of China (Grant No. 81172992) and the National Basic Research Program of China (973 Program, Grant No. 2009CB930300) and Innovation Team of Ministry of Education (Grant No. BMU20110263).

李捷思, 杨科, 柯曦宇, 杜若, 张烜*, 张强. CLA-PTX对黑色素瘤B16-F10的体内外抗肿瘤作用[J]. 中国药学(英文版), 2014, 23(1): 46-53.

Jiesi Li, KeYang, Xiyu Ke, Ruo Du, Xuan Zhang*, Qiang Zhang. In vitro and in vivo antitumor efficacy of CLA-PTX on B16-F10 melanoma cells [J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(1): 46-53.

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CLA-PTX对黑色素瘤B16-F10的体内外抗肿瘤作用

In vitro and in vivo antitumor efficacy of CLA-PTX on B16-F10 melanoma cells

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