Effect of gefitinib on the migration of triple-negative breast cancer cell line MDA-MB-231 cells.
- VernacularTitle:吉非替尼对三阴性乳腺癌细胞MDA-MB-231迁移运动的影响
- Author:
Hong-Meng ZHAO
1
;
Bin ZHANG
;
Yue LI
;
Lin ZHANG
;
Fei ZHANG
;
Yan-Qun SONG
;
Wei-Hong FENG
;
Wen-Feng CAO
;
Xu-Chen CAO
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; administration & dosage; pharmacology; Breast Neoplasms; metabolism; pathology; Cell Line, Tumor; Cell Movement; drug effects; Cytoskeleton; drug effects; Dose-Response Relationship, Drug; Female; Humans; Phosphatidylinositol 3-Kinases; metabolism; Phosphorylation; Protein Kinase Inhibitors; administration & dosage; pharmacology; Proto-Oncogene Proteins c-akt; metabolism; Quinazolines; administration & dosage; pharmacology; Receptor, Epidermal Growth Factor; metabolism; Receptor, ErbB-2; metabolism; Receptors, Estrogen; metabolism; Receptors, Progesterone; metabolism; Signal Transduction; drug effects
- From: Chinese Journal of Oncology 2012;34(2):84-88
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of gefitinib on the migration of triple-negative breast cancer cell line MDA-MB-231 cells.
METHODSGefitinib was used in concentrations of 0 micromol/L, 0.1 micromol/L, 1 micromol/L, 10 micromol/L and 20 micromol/L, respectively. Phosphorylation levels of EGFR and Akt were analyzed by Western blot. The capability of migration was measured by scratch test and Boyden chamber assay. Microfilaments (cell skeleton ) remolding and polarization were evaluated by immunofluorescence microscopy.
RESULTSComparing with the control group (0 micromol/L gefitinib), gefitinib effectively inhibited the phosphorylation of EGFR and its downstream key proteins, and the effect displayed an obvious dose-effect relationship. At 24 hours after wound scratch, the cell migration distance of each group with 0, 0.1, 1, 10, 20 micromol/L gefitinib was (36.3 +/- 4.0) microm, (30.3 +/- 3.8) microm, (26.8 +/- 3.3) microm, (17.0 +/- 2.6) microm, and (11.0 +/- 2.5) microm, respectively. At 3.5 hours after Boyden chamber assay, the cell count of each group with 0, 0.1, 1, 10, 20 micromol/L gefitinib was 69.2 +/- 7.0, 51.8 +/- 7.5, 43.8 +/- 8.7, 30.6 +/- 4.8, and 28.4 +/- 3.4, respectively. Compared with the control group (0 micromol/L gefitinib), gefitinib could significantly prolong the wound-healing time and decrease the migrating cell count (P < 0.05), and significantly inhibit the lamellipodium formation, cell skeleton remolding and changes of the cytoskeleton polarization.
CONCLUSIONSGefitinib can reduce the migration capacity of triple-negative breast cancer cells through inhibiting phosphorylation of EGFR/PI3K/Akt pathway, suppressing the cell skeleton (microfilaments) remolding and changes of its polarization.
