摘要
Considering the results of our previous research that conjugated linoleic acid mixture-paclitaxel （CLA-mixture-PTX） possesses anti-tumor activity against melanoma and brain glioma, the purpose of this study was to investigate the potential anti-tumor efficacy of cis-9, trans- 1 1-conjugated linoleic acid-paclitaxel （c9, tl 1-CLA-PTX） and trans- 1 O, cis- 12-conjugated linoleic acid-paclitaxel （tl0, c12-CLA-PTX） on MCF-7 breast cancer cell line in vitro and in vivo. The in vitro cytotoxicity, apoptosis induction effect and cell cycle arresting effect of c9, t1 1-CLA-PTX and t10, c12-CLA-PTX were investigated. The in vitro cellular uptake of c9, tl 1-CLA-PTX and tl0, cl2-CLA-PTX in MCF-7 cells were also analyzed. Besides, the anti-tumor activity of c9, tl 1-CLA-PTX and tl0, cl2-CLA-PTX was evaluated in MCF-7 tumor bearing nude mice in vivo. The in vitro cytotoxicity results showed that the value of ICs0 of the tl 0, c l2-CLA-PTX is （0.17±0.02） μM, compared with that of （1.08±0.15） μM in CLA-mixture-PTX and （6.50±1.20） μM in c9, tl 1-CLA-PTX treatment group （P〈0.01）. Both tl0, cl2-CLA-PTX and c9, t l 1-CLA-PTX increased the percentage of total apoptotic cells compared with that of control （P〈0.01）. And the rank of apoptosis induction efficacy was t 10, c 12-CLA-PTX〉CLA-mixture-PTX〉c9, t 11-CLA-PTX （P〈0.01）. Compared with untreated cells, the tl0, c12-CLA-PTX and c9, tl 1-CLA-PTX arrested cell cycle progression at the S and G2-M phase. The amount of cellular uptake of t 10, c 12-CLA-PTX was significantly higher than that of CLA-mixture-PTX （P〈0.01）, which was significantly higher than that of c9, t1 1-CLA-PTX （P〈0.01）. The rank of in vivo anti-tumor activity was tl0, c12-CLA-PTX〉CLA-mixture-PTX〉 c9, t1 1-CLA-PTX （P〈0.01）. In conclusion, our study demonstrated that both tl0, cl2-CLA-PTX and c9, tl 1-CLA-PTX has significant anti-tumor activity in MCF-7 cell line. And while c9, tl 1-CLA-PTX showed weaker inhibitory effect than CLA-mixture-PTX, str
在前期研究中,CLA-mixture-PTX展现出了对黑色素瘤与脑胶质瘤一定的抗肿瘤作用。本研究旨在探索c9,t11-CLA-PTX与t10,c12-CLA-PTX对人源乳腺癌MCF-7细胞的体内外抗肿瘤作用。研究中考察了c9,t11-CLA-PTX与t10,c12-CLA-PTX的体外细胞摄取、细胞毒、细胞凋亡,以及细胞周期作用。用荷瘤BALB/c裸鼠研究了c9,t11-CLA-PTX与t10,c12-CLA-PTX的体内抗肿瘤作用。体外细胞毒研究结果表明:t10,c12-CLA-PTX的IC50为(0.17±0.02)μM,显著优于CLA-mixture-PTX(1.08±0.15)μM(P<0.01),后者显著优于c9,t11-CLA-PTX(6.50±1.20)μM(P<0.01)。与空白对照组相比,c9,t11-CLA-PTX与t10,c12-CLA-PTX均可使细胞总凋亡比例增加(P<0.01);和CLA-mixture-PTX组相比,t10,c12-CLA-PTX可使细胞总凋亡比例增加(P<0.01),c9,t11-CLA-PTX则使细胞总凋亡比例降低(P<0.01)。与空白对照组相比,c9,t11-CLA-PTX与t10,c12-CLA-PTX均将细胞周期阻滞于S期与G2-M,与CLA-mixture-PTX相同。t10,c12-CLA-PTX的细胞摄取量显著高于CLA-mixture-PTX(P<0.01),后者的细胞摄取量显著高于c9,t11-CLA-PTX(P<0.01)。体内抗肿瘤药效研究结果显示,t10,c12-CLA-PTX的抗肿瘤活性显著高于空白对照组和CLA-mixture-PTX组(P<0.01),而c9,t11-CLA-PTX的抗肿瘤活性仅高于空白对照组(P<0.01)。上述结果表明,t10,c12-CLA-PTX对MCF-7细胞有显著体内外抗肿瘤作用,可以作为CLA-mixture-PTX的替代药物进行后续研究。
基金
National Natural Science Foundation of China (Grant No.81172992)
the National Basic Research Program of China (973 Program,Grant No.2013CB932501)
Innovation Team of Ministry of Education (Grant No.BMU20110263)
