Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

28 September 2012

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

Yinghui ChenAE, Yongbo ZhaoBD, Cuicui WangC, Xia XiaoB, Xiaoyong ZhouC, Guoxiong XuAEF

DOI: 10.12659/MSM.883477

Med Sci Monit 2012; 18(10): BR383-388

Abstract

Background: Several studies have shown that multidrug transporters, such as P-glycoprotein (PGP), are involved in cell resistance to chemotherapy and refractory epilepsy. The p38 mitogen-activated protein kinase (MAPK) signaling pathway may increase PGP activity. However, p38-mediated drug resistance associated with PGP is unclear. Here, we investigated p38-mediated doxorubicin-induced drug resistance in human leukemia K562 cells.
Material/Methods: The expression of PGP was detected by RT-PCR, Western blot, and immunocytochemistry. Cell viability and half-inhibitory concentrations (IC50) were determined by CCK-8 assay. The intracellular concentration of drugs was measured by HPLC.
Results: A doxorubicin-induced PGP overexpression cell line, K562/Dox, was generated. The p38 inhibitor SB202190 significantly decreased MDR1 mRNA expression, as well as PGP, in K562/Dox cells. The IC50 of phenytoin sodium and doxorubicin in K562/Dox cells was significantly higher than that in wild-type K562 cells, indicating the drug resistance of K562/Dox cells. During the blocking of p38 activity in the presence of SB202190, cell number was significantly reduced after the phenytoin sodium and doxorubicin treatment, and the IC50 of phenytoin sodium and doxorubicin was decreased in K562/Dox cells. HPLC showed that the intracellular levels of phenytoin sodium and doxorubicin were significantly lower in K562/Dox cells than those in K562 cells. The decrease of the intracellular level of these drugs was significantly abolished in the presence of SB202190.
Conclusions: Our study demonstrated that p38 is, at least in part, involved in doxorubicin-induced drug resistance. The mechanistic study of MAPK-mediated PGP and the action of SB202190 need further investigation.

Keywords: Phenytoin - pharmacology, P-Glycoprotein - metabolism, Leukemia - pathology, K562 Cells, Drug Resistance, Neoplasm - drug effects, Doxorubicin - pharmacology, Dose-Response Relationship, Drug, Cell Survival - drug effects, Protein Kinase Inhibitors - pharmacology, p38 Mitogen-Activated Protein Kinases - metabolism

Add Comment 0 Comments

Editorial

01 February 2025 : Editorial  

Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-Smokers

Dinah V. Parums

DOI: 10.12659/MSM.948255

Med Sci Monit 2025; 31:e948255

0:00

Most Viewed Current Articles

17 Jan 2024 : Review article   6,969,932

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

16 May 2023 : Clinical Research   701,896

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Mar 2024 : Editorial   25,741

Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...

DOI :10.12659/MSM.944204

Med Sci Monit 2024; 30:e944204

0:00

28 Jan 2024 : Review article   20,253

A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and Future

DOI :10.12659/MSM.943912

Med Sci Monit 2024; 30:e943912

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750