Effect of nobiletin on invasion and migration abilities in human breast cancer MDA-MB-231 cells
10.13699/j.cnki.1001-6821.2017.05.014
- VernacularTitle:川皮苷对人乳腺癌MDA-MB-231细胞侵袭转移能力的影响
- Author:
Xiao-Hui DU
1
;
Zhu-Jun SHEN
;
Jia-Xin YUAN
;
Qi ZHANG
;
Hong-Xia CUI
Author Information
1. 齐齐哈尔医学院药理教研室
- Keywords:
nobiletin;
human breast cancer cells of MDA-MB-231;
invasion;
matrix metalloproteinases;
mitogen activated protein kinase
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(5):435-438,447
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of nobiletin on the invasion and migration capabilities of breast cancer MDA-MB-231 cells.Methods One blank group and 5 concentrations of (nobiletin 12.5,25,50,100,200 μmol · L-1) experimental groups were set up.The 3 -(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide was used to observe the effects of different concentrations of nobiletin on proliferation of human breast cancer cell line MDA-MB-231.Transwell chamber and wound healing assay were used to detect the effects of nobiletin on the migration and invasion of MDA-MB-231.The cyclooxygenase 2 (COX-2),matrix metalloproteinase-2 (MMP-2),matrix metalloproteinases-9 (MMP-9),and mitogen activated protein kinase (MAPK) signal pathway related protein expressions were analyzed with Western blot.Results The proliferation of human breast cancer cell line MDA-MB-231 was inhibited by nobiletin in a dose-and time-dependent manner.The OD570 nm of two different concentrations (30,50 mol · L-1) were 0.32 ± 0.02 and 0.27 ± 0.01,compared with the blank group 0.62 ± 0.07,the difference was statistically significant (P < O.05).After working 24 h with nobiletin,migration distances of three different concentrations (10,30,50 mol · L-1) were (75.52 ± 0.69) μm,(111.73 ± 23.12) μm,(115.71 ± 28.09) μm,it obviously increased compared with the blank group (47.03 ± 8.29) μm,the difference was statistically significant (P < 0.05).The expression of MMP-2 in three different concentrations of nobiletin were (14.17 ± 5.26) × 103,(9.33 ± 1.76) × 103,(9.28 ± 1.76) × 103 respectively,compared with the blank group (22.51 ±0.90) × 103,the differences in the last two groups were statistically significant (both P <0.001).Similarly,expression of MMP-9 were (16.82 ±2.38) ×103,(9.91 ±2.08) ×103,(8.86 ±3.26) × 103 respectively,compared with the blank group (21.94 ± 1.50) × 103,the differences were statistically significant (P < 0.05,P < 0.01,P < 0.01).The expression of JNK in three concentrations of nobiletin were (11.78 ± 3.59) × 103,(8.65 ± 1.89) × 103,(6.21 ± 0.60) × 103 respectively,compared with the blank group (13.26 ±2.69) × 103,the difference of high concentration was statistically significant (P < 0.05).Similarly,the expression of p38MAPK were (11.05 ± 0.42) × 103,(10.08 ± 0.83) × 103,(6.94 ± 0.14) × 103 respectively,compared with the blank group (12.38 ± 0.14) × 103,the differences of three concentrations were statistically significant (P <0.01,P < 0.01,P < 0.001).Conclusion Nobiletin has a certain role in inhibiting the invasion and migration of MDA-MB-231 cells in vitro,and its mechanism may be related to the down-regulation of MAPK signaling pathway and inhibiting the expression of MMP-2,MMP-9 and so on.