Reversal effect of mifepristone on adriamycin resistance in human breast cancer cell line MCF-7/ADM in vitro and in vivo.
10.3969/j.issn.1672-7347.2010.06.007
- Author:
Junhui HUANG
1
;
Yi ZHANG
;
Yuting HUANG
;
Xibei ZHANG
;
Jia XIAO
Author Information
1. Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China. hjhmail@xysm.net
- Publication Type:Journal Article
- MeSH:
Animals;
Breast Neoplasms;
pathology;
Cell Line, Tumor;
Doxorubicin;
pharmacology;
Drug Resistance, Neoplasm;
drug effects;
Female;
Humans;
Mice;
Mice, Nude;
Mifepristone;
pharmacology;
Neoplasm Transplantation;
Random Allocation
- From:
Journal of Central South University(Medical Sciences)
2010;35(6):576-583
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the reversal effect of mifepristone(MIF) on adriamycin(ADM) resistance in human breast cell line MCF-7/ADM in vitro and in vivo.
METHODS:The transplantable models of MCF-7 cells resisting against adriamycin were established in nude mice by subcutaneous implantation to observe the reversal effect of MIF in vivo. The mice were randomly divided into 4 groups: a control group(treated with saline water 0.2 mL intraperitoneally and edible oil 0.5 mL orally), an MIF group (treated with mifepristone 30 mg/kg orally and saline water 0.2 mL intraperitoneally), an ADM group (treated with adriamycin 5 mg/kg intraperitoneally and edible oil 0.5 mL orally) and an ADM+MIF group (treated with ADM 5mg/kg intraperitoneally and mifepristone 30 mg/kg orally every 3 days). Tumor changes were investigated after different drug treatments. The reversal effect of 5 micromol/L MIF in vitro on the ADM resistance cell line MCF-7/ADM and non ADM resistance cell line MCF-7 was determined by 4,5-dimethylthiazol-2-yl (MTT) assay.
RESULTS:(1) The inhibitory rate of 5 micromol/L of MIF for both cell lines MCF-7 and MCF-7/ADM was less than 5%, and it had no statistical difference compared with the group that was not treated with MIF(P > 0.05). (2) ADM could inhibit the growth of both MCF-7 and MCF-7/ADM,but the inhibition concentration 50 (IC(50)) of MCF-7 (0.42 mg/L) was obviously less than that of MCF-7/ADM(17.21 mg/L) (P < 0.05). (3) IC(50) of MCF-7/ADM of MIF+ADM group was 1.96 mg/L in vitro, which was significantly less than that in ADM alone group(17.21 mg/L) (P < 0.05), and 5 micromol/L of MIF reversed ADM resistance with fold-reversal of 8.78. (4) MIF had some effect on the inhibition of MCF-7/ADM cell growth in vivo, the xenograft volume in the MIF+ADM group [(232.5149 +/- 309.2377) mm(3)] was significantly smaller than that in the control group[(962.2309 +/- 261.1313) mm(3) ] after the 4 week treatment(P<0.05), and also smaller than that in the MIF group [(778.2846 +/- 42.6919) mm(3)] and in the ADM group [(508.9648 +/- 16.2609) mm(3)](P < 0.05). There was significant inhibition on xenograft weight after MIF combined with ADM treatment in vivo, and the inhibitory rate was 78.0%.
CONCLUSION:MIF can effectively reverse ADM resistance in human breast cancer cell line MCF-7/ADM both in vitro and in vivo.
