scholarly journals Inhibition of p38 MAPK diminishes doxorubicin-induced drug resistance associated with P-glycoprotein in human leukemia K562 cells

2012 ◽  
Vol 18 (10) ◽  
pp. BR383-BR388 ◽  
Author(s):  
Yinghui Chen ◽  
Yongbo Zhao ◽  
Cuicui Wang ◽  
Xia Xiao ◽  
Xiaoyong Zhou ◽  
...  
Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 929-929
Author(s):  
Ping Liu ◽  
Liting Guo ◽  
Fei Wang ◽  
Guohua Xia ◽  
Yonglu Wang ◽  
...  

Abstract Drug resistance is a major obstacle in cancer chemotherapy, especially in the treatment of leukemia. Hypoxia is an inseparable component of the solid tumor microenvironment as well as the bone marrow (BM) microenvironment. In this study, we investigated the effect of the new nanoparticles polyethylene glycol (PEG)-poly L-lysine (PLL)-poly lactic-co-glycolic acid (PLGA) (PEG-PLL-PLGA) modified by transferrin (Tf) combined with daunorubicin (DNR) on K562 cells under hypoxia. We found the IC50 of DNR and DNR-PEG-PLL-PLGA in K562 cells increased under hypoxia, while the IC50 of DNR-Tf-PEG-PLL-PLGA in K562 cells decreased under hypoxia according to the results of MTT assay. The apoptosis of cells and the intracellular concentration of DNR were detected by flow cytometry (FCM). From the datas, we found that the new targeted nanoparticles can overcome hypoxia induced drug resistance of K562 cells. By targeting the transferrin receptor (TfR) on the surface of K562 cells, the new targeted drug led to an increase in intracellular accumulation of DNR. Transcription and Protein of P-glycoprotein (P-gp) and TfR increased in K562 cells under hypoxia, which probably had a relationship with the decreased degradation of the Hypoxia-Inducible Factor-1α (HIF-1α). We further detected the levels of HIF-1α, Bcl-2, Bax and Caspase-3 of K562 cells in transcription and protein under hypoxia regulated by DNR, DNR-PEG-PLL-PLGA and DNR-Tf-PEG-PLL-PLGA, respectively. DNR-Tf-PEG-PLL-PLGA had the best effect when compared with other groups. Furthermore, intravenous injection of DNR-Tf-PEG-PLL-PLGA expressed the best effect of suppressing proliferation of K562 cells injected to nude mice among the three drugs. Therefore, the new drug DNR-Tf-PEG-PLL-PLGA may be a potential cancer therapy for human leukemia. Disclosures No relevant conflicts of interest to declare.


2015 ◽  
Vol 284 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Jung-Jung Changchien ◽  
Ying-Jung Chen ◽  
Chia-Hui Huang ◽  
Tian-Lu Cheng ◽  
Shinne-Ren Lin ◽  
...  

Toxicon ◽  
2010 ◽  
Vol 55 (7) ◽  
pp. 1306-1316 ◽  
Author(s):  
Ying-Jung Chen ◽  
Wen-Hsin Liu ◽  
Pei-Hsiu Kao ◽  
Jeh-Jeng Wang ◽  
Long-Sen Chang

1993 ◽  
Vol 16 (10) ◽  
pp. 1054-1056
Author(s):  
Dai SASAKI ◽  
Satoshi KOSUNAGO ◽  
Takeshi MIKAMI ◽  
Tatsuji MATSUMOTO ◽  
Masuko SUZUKI

2012 ◽  
Vol 599 ◽  
pp. 71-75
Author(s):  
Shu Li Shao ◽  
Bin Zhao ◽  
Wei Wei Zhang ◽  
Wei Zhao ◽  
Guang Hui Wu ◽  
...  

Objective: The research aimed to study the effects of mitomycin on human leukemic K562 cells, and to explore the mechanism of mitomycin induced apoptosis.In order to provide previous experiment basis for mitomycin applying clinical treatments Methods: The multiplication and apoptosis status of K562 cells treated different time by different concentration mitomycin were observed by light microscope, fluorescence microscope, TEM, agrose gel electrophoresis of DNA and flow cytometry. Results: The results showed that mitomycin could induce K562 cells apoptosis, and the best concentration was 12.5μg/ml for 48 h. The optimal concentration of apoptosis induced by apoptosis rate is (28.8±1.04)% (P<0.01). Mitomycin could affect the S phase among cellular multiplication, cell could be blocked by mitomycin and then apoptosis in this phase. Conclusions: Mitomycin can induce the apoptosis of human leukemic K562 cells. It is of great significance to guide clinical medication.


Molecules ◽  
2015 ◽  
Vol 20 (7) ◽  
pp. 11981-11993 ◽  
Author(s):  
Jianping Fan ◽  
Pan Wang ◽  
Xiaobing Wang ◽  
Wei Tang ◽  
Chunliang Liu ◽  
...  

2008 ◽  
Vol 1780 (5) ◽  
pp. 757-763 ◽  
Author(s):  
Un-Ho Jin ◽  
Ki-Tae Ha ◽  
Kyung-Woon Kim ◽  
Young-Chae Chang ◽  
Young-Coon Lee ◽  
...  

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