Abstract:
Objective To study the relevance between CYP1B1 expression and paclitaxel resistance in human breast cancer cell line.
Methods Using human breast cancer cell line MCF-7 as model to observe the effect of CYP1B1 expression which induced by 2,3, 7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on paclitaxel resistance. To observe if pacilitaxel resistance of MCF-7 is specifically induced by CYP1B1 expression. We treated MCF-7 with CYP1B1 specific inhibitorct-naphthoflavone combined with paclitaxel. RT-PCR was used to detect the CYP 1B 1 mRNA expression; CYP 1B 1 protein expression was detected by cell immunochemical staining and Western blotting. The cytotoxicity ofpaclitaxel was assayed by MTS method.
Results TCDD can induce human breast cancer cell line MCF-7 stably express CYP1B1, CYP1B1 mRNA and protein expression have dose dependency with the concentration of TCDD(P < 0.05);Paclitaxel can not induce MCF-7 cell line express CYP 1B 1.Treated MCF-7 cell line with paclitaxel at different concentration (0.01-0.1 μg/ml), the inhibitory rate of paclitaxel on CYP1B1 expression group was reduced significantly(P < 0.05), compared with control group. This paclitaxel resistance can be reversed by 10 μmol/L ANF.
Conclusion In human breast cell line MCF-7, CYP 1B 1 expression which was induced by TCDD can increase tumor cells survival and lead to paclitaxel resistance.