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 GE-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 B 16-F 10 cell line.
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