The anti-tumor efficacy of c9,tll-CLA-PTX and t10, c12-CLA-PTX on MCF-7 breast cancer cells: in vitro and in vivo

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-11 -conjugated linoleic acid-paclitaxel (c9, tll-CLA-PTX) and trans-10, cis-12-conjugated linoleic acid-paclitaxel (t10, 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,t11-CLA-PTX and t10, c12-CLA-PTX were investigated. The in vitro cellular uptake of c9, tll-CLA-PTX and t10, c12-CLA-PTX in MCF-7 cells were also analyzed. Besides, the anti-tumor activity of c9, t11-CLA-PTX and t10, c12-CLA-PTX was evaluated in MCF-7 tumor bearing nude mice in vivo. The in vitro cytotoxicity results showed that the value of IC_(50) of the t10,c12-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, tll-CLA-PTX treatment group (P<0.01). Both t10, c12-CLA-PTX and c9, tll-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 t10, c12-CLA-PTX>CLA-mixture-PTX>c9, tll-CLA-PTX (P<0.01). Compared with untreated cells, the t10, c12-CLA-PTX and c9, tll-CLA-PTX arrested cell cycle progression at the S and G_2-M phase. The amount of cellular uptake of t10, c12-CLA-PTX was significantly higher than that of CLA-mixture-PTX (P<0.01), which was significantly higher than that of c9, tll-CLA-PTX (P<0.01). The rank of in vivo anti-tumor activity was t10, c12-CLA-PTX>CLA-mixture-PTX>c9, tll-CLA-PTX (P<0.01). In conclusion, our study demonstrated that both t10, x12-CLA-PTX and c9, tll-CLA-PTX has significant anti-tumor activity in MCF-7 cell line. And while c9,tll-CLA-PTX showed weaker inhibitory effect than CLA-mixture-PTX, stronger inhibitory effect was presented by t10, c12-CLA-PTX, which could be a promising alternative for CLA-mixture-PTX.National Natural Science Foundation of China,the National Basic Research Program of China (973 Program),Innovation Team of Ministry of Education中国科学引文数据库(CSCD)11751-7592