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Effect of phosphatase and tensin homology deleted on chromosome 10 (PTEN) gene transfection on reversal of multidrug resistance in K562/ADM cells.
Leuk Lymphoma. 2012 Jul; 53(7):1383-9.LL

Abstract

The phosphatase and tensin homology deleted on chromosome 10 (PTEN) gene is a novel tumor suppressor gene of the phosphatase family. Studies have shown that the PTEN gene is probably involved in human malignant disease pathogenesis, multidrug resistance, angiogenesis and extramedullary infiltration. This study was designed to investigate the effect of wild-type PTEN gene transfection on drug resistance reversal in K562/ADM leukemia cells in vitro and the possible mechanism. A recombinant adenovirus containing green fluorescent protein gene and wild-type PTEN gene (Ad-PTEN-GFP) or a recombined adenovirus containing green fluorescent protein gene only (Ad-GFP) was transfected into K562/ADM cells. These cells were then treated with different concentrations of adriamycin, cytarabine or arsenic trioxide, respectively. The half-maximal inhibitory concentration (IC(50)) of each drug was detected by MTT assay and the drug resistance reversal factor (RF) was calculated. The proliferation inhibition rate of these K562/ADM cells treated with or without the above-mentioned drugs was determined by MTT assay and the apoptosis rate was evaluated by flow cytometry. PTEN, nuclear factor-κB (NF-κB), I-κB, p53, multidrug resistance genes MDR1 and MRP, and apoptosis related genes Bcl-2, Bcl-xL and Bax mRNA levels were detected by real-time fluorescence relative-quantification reverse transcription polymerase chain reaction (FQ-PCR). PTEN, Akt, p-Akt and NF-κB (p65) protein levels were detected by Western blot. Results showed that PTEN gene transfection could increase the sensitivity of K562/ADM cells to chemotherapeutic drugs. The drug resistance reversal index of adriamycin, cytarabine and arsenic trioxide was 3.8-fold, 2.65-fold and 2.64-fold, respectively, after PTEN gene transfection. NF-κB, MDR1, Bcl-2 and Bcl-xL mRNA levels as well as p-Akt and NF-κB (p65) protein levels were down-regulated, while p53 and Bax mRNA levels were up-regulated in K562/ADM cells after transfection with Ad-PTEN-GFP. Therefore, wild-type PTEN gene transfection might increase drug sensitivity or reverse drug resistance via inhibiting the PI3K/Akt pathway and regulating downstream molecules of the cell signaling transduction pathway in K562/ADM cells, such as down-regulating NF-κB, MDR1, Bcl-2 expression but up-regulating the expression of p53 and Bax.

Authors+Show Affiliations

Department of Hematology, The First (No. 1) Hospital of Baoding, Baoding, P R China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22185283

Citation

Cheng, Zhiyong, et al. "Effect of Phosphatase and Tensin Homology Deleted On Chromosome 10 (PTEN) Gene Transfection On Reversal of Multidrug Resistance in K562/ADM Cells." Leukemia & Lymphoma, vol. 53, no. 7, 2012, pp. 1383-9.
Cheng Z, Yang N, Liang W, et al. Effect of phosphatase and tensin homology deleted on chromosome 10 (PTEN) gene transfection on reversal of multidrug resistance in K562/ADM cells. Leuk Lymphoma. 2012;53(7):1383-9.
Cheng, Z., Yang, N., Liang, W., Yan, X., Li, L., & Pan, L. (2012). Effect of phosphatase and tensin homology deleted on chromosome 10 (PTEN) gene transfection on reversal of multidrug resistance in K562/ADM cells. Leukemia & Lymphoma, 53(7), 1383-9. https://doi.org/10.3109/10428194.2011.650695
Cheng Z, et al. Effect of Phosphatase and Tensin Homology Deleted On Chromosome 10 (PTEN) Gene Transfection On Reversal of Multidrug Resistance in K562/ADM Cells. Leuk Lymphoma. 2012;53(7):1383-9. PubMed PMID: 22185283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of phosphatase and tensin homology deleted on chromosome 10 (PTEN) gene transfection on reversal of multidrug resistance in K562/ADM cells. AU - Cheng,Zhiyong, AU - Yang,Ning, AU - Liang,Wentong, AU - Yan,Xiaoyan, AU - Li,Lin, AU - Pan,Ling, Y1 - 2012/01/31/ PY - 2011/12/22/entrez PY - 2011/12/22/pubmed PY - 2012/10/31/medline SP - 1383 EP - 9 JF - Leukemia & lymphoma JO - Leuk Lymphoma VL - 53 IS - 7 N2 - The phosphatase and tensin homology deleted on chromosome 10 (PTEN) gene is a novel tumor suppressor gene of the phosphatase family. Studies have shown that the PTEN gene is probably involved in human malignant disease pathogenesis, multidrug resistance, angiogenesis and extramedullary infiltration. This study was designed to investigate the effect of wild-type PTEN gene transfection on drug resistance reversal in K562/ADM leukemia cells in vitro and the possible mechanism. A recombinant adenovirus containing green fluorescent protein gene and wild-type PTEN gene (Ad-PTEN-GFP) or a recombined adenovirus containing green fluorescent protein gene only (Ad-GFP) was transfected into K562/ADM cells. These cells were then treated with different concentrations of adriamycin, cytarabine or arsenic trioxide, respectively. The half-maximal inhibitory concentration (IC(50)) of each drug was detected by MTT assay and the drug resistance reversal factor (RF) was calculated. The proliferation inhibition rate of these K562/ADM cells treated with or without the above-mentioned drugs was determined by MTT assay and the apoptosis rate was evaluated by flow cytometry. PTEN, nuclear factor-κB (NF-κB), I-κB, p53, multidrug resistance genes MDR1 and MRP, and apoptosis related genes Bcl-2, Bcl-xL and Bax mRNA levels were detected by real-time fluorescence relative-quantification reverse transcription polymerase chain reaction (FQ-PCR). PTEN, Akt, p-Akt and NF-κB (p65) protein levels were detected by Western blot. Results showed that PTEN gene transfection could increase the sensitivity of K562/ADM cells to chemotherapeutic drugs. The drug resistance reversal index of adriamycin, cytarabine and arsenic trioxide was 3.8-fold, 2.65-fold and 2.64-fold, respectively, after PTEN gene transfection. NF-κB, MDR1, Bcl-2 and Bcl-xL mRNA levels as well as p-Akt and NF-κB (p65) protein levels were down-regulated, while p53 and Bax mRNA levels were up-regulated in K562/ADM cells after transfection with Ad-PTEN-GFP. Therefore, wild-type PTEN gene transfection might increase drug sensitivity or reverse drug resistance via inhibiting the PI3K/Akt pathway and regulating downstream molecules of the cell signaling transduction pathway in K562/ADM cells, such as down-regulating NF-κB, MDR1, Bcl-2 expression but up-regulating the expression of p53 and Bax. SN - 1029-2403 UR - https://www.unboundmedicine.com/medline/citation/22185283/Effect_of_phosphatase_and_tensin_homology_deleted_on_chromosome_10__PTEN__gene_transfection_on_reversal_of_multidrug_resistance_in_K562/ADM_cells_ L2 - https://www.tandfonline.com/doi/full/10.3109/10428194.2011.650695 DB - PRIME DP - Unbound Medicine ER -