Annexin A1 increases the sensitivity of K562 cell to imatinib.
- Author:
Kang-Ning LI
1
;
Jing JIN
;
Xiao-Guang CHEN
Author Information
1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Actins;
metabolism;
Annexin A1;
genetics;
metabolism;
Antineoplastic Agents;
pharmacology;
Cell Proliferation;
drug effects;
Drug Resistance, Neoplasm;
Fusion Proteins, bcr-abl;
metabolism;
Humans;
Imatinib Mesylate;
pharmacology;
Immunoprecipitation;
K562 Cells;
Mitogen-Activated Protein Kinase 3;
metabolism;
Transfection;
src-Family Kinases;
metabolism
- From:
Acta Pharmaceutica Sinica
2013;48(6):866-873
- CountryChina
- Language:Chinese
-
Abstract:
Annexin A1 (ANXA1) is a kind of endogenous scaffold protein. Previous research showed that ANXA1 could increase markedly with multiple increase of drug resistance in K562/imatinib cell lines in vitro. Here the stable transfection cell strains K562-pEGFP-N1 which was the native control and K562-pEGFP-N1-ANXA1 which can stably express ANXA1 were established using the Lipofectamine 2000 in order to find whether ANXA1 involved in the drug resistance. Cell growth inhibition experiment via MTT and cell proliferation experiment via MTS showed that K562-pEGFP-N1-ANXA1 cell strain was more sensitive to imatinib than the K562-pEGFP-N1 cell strain, and however the ability of proliferation of K562-pEGFP-N1-ANXA1 cell strain did not change compared with the negative control. Western blotting results showed that the expression of proteins in Annexin family did not change; drug resistance proteins, Bcr-Abl/p-Bcr-Abl (Tyr245), Src family kinase for example, did not change; proteins related with cell proliferation and cell cycle, such as ERK1/2MAPK, p-38MAPK, CDK1 and Wee 1, did not change either in the K562-pEGFP-N1-ANXA1 cell strain compared with the negative control. The co-immunoprecipitation result showed that the interaction between ANXA1 and beta-actin in the K562-pEGFP-N1-ANXA1 cell strain increased markedly. The deduction was that ANXA1 may make the K562-pEGFP-N1-ANXA1 cell strain more sensitive to imatinib due to the increased uptake of imatinib via the increase of ANXA1 and the interaction between ANXA1 and beta-actin in the K562-pEGFP-N1-ANXA1 cell strain in vitro.
