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Reversal effect of PI3-K inhibitor LY294002 on P-glycoprotein-mediated multidrug resistance of human leukemia cell line K562/DNR and gastric cancer cell line SGC7901/ADR.
- Source :
-
Ai zheng = Aizheng = Chinese journal of cancer [Ai Zheng] 2009 Feb; Vol. 28 (2), pp. 97-9. Date of Electronic Publication: 2009 Feb 23. - Publication Year :
- 2009
-
Abstract
- Background and Objective: Phosphatidylinositol-3-kinase/protein kinase B (PI3-K/Akt) signaling pathway plays an important role in cell survival. This study was to explore the reversal effect of PI3-K inhibitor LY294002 on p-glycoprotein (P-gp)-mediated multidrug resistance in human leukemia cell line K562/DNR and gastric cancer cell line SGC7901/ADR.<br />Methods: The cells were divided into simple drug-treated groups and LY294002 pretreated groups: the former groups received treatment of daunorubicin (DNR), adriamycin (ADR), vincristine (VCR) and etoposide (VP-16), respectively; the latter groups received pretreatment of LY294002 before drug treatment. Trypan blue dye exclusion method and MTT assay were used to detect the drug sensitivity of K562/DNR and SGC7901/ADR cells, and the effect of LY294002 on the drug resistance. The expression of P-gp and phosphorylated Akt (p-Akt) in K562/DNR, SGC7901/ADR and their parental cell lines K562 and SGC7901 was detected by Western blot. Intracellular drug accumulation was measured by flow cytometry (FCM).<br />Results: LY294002 pretreatment significantly decreased the 50% inhibition concentration (IC(50)) of DNR, ADR, VCR and VP-16 for K562/DNR cells, with reverse efficiencies of 72.4%, 64.9%, 60.4% and 52.8%. In SGC7901/ADR cells, the similar result was obtained with a reverse efficiency of 31.0%. LY294002 pretreatment partially inhibited the expression of p-Akt and P-gp, and promoted the intracellular accumulation of DNR and ADR in K562/DNR and SGC7901/ADR cells, respectively.<br />Conclusion: LY294002 could partially reverse multidrug resistance in K562/DNR and SGC7901/ADR cells in vitro via inhibiting PI3-K/Akt pathway.
- Subjects :
- Antineoplastic Agents pharmacology
Blotting, Western
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Daunorubicin pharmacology
Dose-Response Relationship, Drug
Doxorubicin pharmacology
Enzyme Inhibitors pharmacology
Etoposide pharmacology
Humans
K562 Cells
Leukemia metabolism
Leukemia pathology
Proto-Oncogene Proteins c-akt metabolism
Stomach Neoplasms metabolism
Stomach Neoplasms pathology
Vincristine pharmacology
ATP Binding Cassette Transporter, Subfamily B metabolism
Chromones pharmacology
Drug Resistance, Multiple drug effects
Drug Resistance, Neoplasm drug effects
Morpholines pharmacology
Phosphoinositide-3 Kinase Inhibitors
Subjects
Details
- Language :
- English
- Volume :
- 28
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Ai zheng = Aizheng = Chinese journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 19550116