Effects of c-Met inhibitor SU11274 on basal-like breast cancer cells MDA-MB-231
10.3760/cma.j.issn.1007-631X.2012.03.021
- VernacularTitle:c-Met抑制剂SU11274对基底样乳腺癌MDA-MB-231细胞的影响
- Author:
Weihong FENG
;
Bin ZHANG
;
Yuanyuan LI
;
Hongmeng ZHAO
;
Yue ZHANG
;
Zujin CHEN
;
Bowen LIU
;
Xuchen CAO
- Publication Type:Journal Article
- Keywords:
Breast neoplasms;
Carcinoma,basal cell;
Proto-oncogene proteins c-met;
Apoptosis
- From:
Chinese Journal of General Surgery
2012;27(3):234-237
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of a new c-Met inhibitor SU11274 on apoptosis and motility of c-Met-positive basal-like breast cancer cells MDA-MB-231. Methods The concentrations of SUl1274 were set to 0,0.1,1,10 and 20 μmol/L.Morphological change of apoptotic cells was analyzed by Hoechst33342,MitroTrackerRed and Yo-pro-1 staining.The apoptotic rate of MDA-MB-231 cells were determined by Annexin V/PI double-staining. The expression of apoptosis related proteins (Bcl-XL,Caspase-3 and PARP) and phosphorylation levels of c-Met and Akt were analyzed by Western blot.The capability of motility were measured by wound-healing assay and chemotaxis assay. Results After treatment by SU11274( 10 μmol/L) for 48 h,shrinking apoptotic cells of MDA-MB-231 was observed by flurescent microscope and nuclear fragmentation was seen.Annexin V/PI double-staining showed SU11274induced apoptosis of MDA-MB-231 cells (P ＜ 0.05 ),and the apoptotic rates were (7.3 ± 0.9) ％,( 14.1 ±0.6) ％,(35.5 ± 4.4) ％ and (48.2 ± 5.3 ) ％,respectively.SU11274 downregulated the expression of Bcl-XL and promoted the dissection of Caspase-3 and PARP in a dose dependent relationship.SU11274 prolongs the wound-healing time,decreases the migration cell count (P ＜ 0.05 ) and effectively inhibits the phosphorylation of c-Met and its downstream key proteins Akt in a dose-dependent manner.Conclusions C-Met inhibitor SU11274 induces apoptosis and inhibits the motility of c-Met-positive basallike breast cancer cell line MDA-MB-231,probably through inhibiting phosphorylation of c-Met/PI3K/Akt.
