Please wait a minute...

中国生物工程杂志

China Biotechnology
China Biotechnology  2013, Vol. 33 Issue (3): 54-60    DOI:
    
Mechanism of PTEN/NF-κB/Caspase Pathway on Adriamycin Resistance Reversal in K562/ADM Cells
CHENG Zhi-yong1, LIANG Wen-tong1, WANG Su-yun2, YAN Xiao-yan1, LI Hua1, WANG Bao-yan1, TIAN He1, WEI Yu-tao1, LU Xi 1
1. The No1 Hospital of Baoding, Baoding 071000, China;
2. Hebei General Hospital, Shijiazhuang 050051, China
Download: HTML   PDF(903KB) HTML
Export: BibTeX | EndNote (RIS)      

Abstract  Objective:To investigate the mechanism of PTEN/Akt/NF-κB signal pathway in drug resistance reversal on K562/ADM cells in vitro. Methods: The recombinated adenovirus containing green fluorescent protein and PTEN(Ad-PTEN-GFP)or empty vector (Ad-GFP) was transfected into K562/ADM cells together with different concentration of adriamycin(ADM). We detected the different drug IC50 with or without PTEN gene transfection to calculate the durg resistant factor (RF) by MTT; the proliferation of K562/ADM cells was observed by MTT assay; the apoptosis rate was assessed by flow cytometry (FCM). PTEN, NF-κB, I-κB, P53 mRNA were detected by real-time fluorescent relative-quantification reverse transcriptional PCR (FQ-PCR). PTEN, Akt, p-Akt and NF-κB protein levels were detected by western blot. Results: PTEN gene can enhance adriamycin sensitive in K562/ADM cells. The RF of ADM was 3.8 fold after transfection with PTEN gene. p-Akt and NF-Κb (P65) protein levels were down-regulated and NF-κB mRNA down-regulated too, but P53 up-regulated after transfaction with Ad-PTEN-GFP in K562/ADM cells, Caspase-3/7 activities up-regulated. PTEN mRNA expression levels were negative correlation with NF-κB mRNA(r=-0.968,P<0.05), NF-κB activities were negative correlation with Caspase-3/7 activities(r=-0.986,P<0.05). Conclusion: Wild PTEN gene might reverse adriamycin resistance via inhibiting PTEN/NF-κB/Caspase pathway.

Key wordsPTEN      PI3K/Akt      Drug resistance      Transcription factor      NF-κB     
Received: 08 October 2012      Published: 25 March 2013
ZTFLH:  R733  
Cite this article:

CHENG Zhi-yong, LIANG Wen-tong, WANG Su-yun, YAN Xiao-yan, LI Hua, WANG Bao-yan, TIAN He, WEI Yu-tao, LU Xi. Mechanism of PTEN/NF-κB/Caspase Pathway on Adriamycin Resistance Reversal in K562/ADM Cells. China Biotechnology, 2013, 33(3): 54-60.

URL:

https://manu60.magtech.com.cn/biotech/     OR     https://manu60.magtech.com.cn/biotech/Y2013/V33/I3/54

[1] Lin X, Zhang X, Wang Q,et al.Perifosine downregulates MDR1 gene expression and reverses multidrug-resistant phenotype by inhibiting PI3K/Akt/NF-κB signaling pathway in a human breast cancer cell line. Neoplasma. 2012;59(3):248-256.
[2] Han Z, Hong L, Han Y,et al. Phospho Akt mediates multidrug resistance of gastric cancer cells through regulation of P-gp, Bcl-2 and Bax. J Exp Clin Cancer Res. 2007;26(2):261-268.
[3] Morishita N, Tsukahara H, Chayama K, et al.Activation of Akt is associated with poor prognosis and chemotherapeutic resistance in pediatric B-precursor acute lymphoblastic leukemia. Pediatr Blood Cancer. 2012;59(1):83-89.
[4] 成志勇,张昕,王哲,等. PTEN和COX-2在髓系白血病中的表达及作用机制探讨.中华检验医学杂志,2012,35(2):165-169. Cheng Z Y, Zhang X, Wang Z. et al. The expression and mechanism of PTEN and COX-2 in myeloid leukemia cells. Chinese Journal of Laboratory Medicine, 2012,35(2):165-169.
[5] Vasudevan K M, Gurvmunhy S, Rangnekar V M. Suppression of PTEN expression by NF-kappaB prevents apoptosis. Mol Cell Biol, 2004,24(3):1007-1021.
[6] Jotta P Y, Ganazza M A, Silva A, et al.Negative prognostic impact of PTEN mutation in pediatric T-cell acute lymphoblastic leukemia. Leukemia. 2010,24(1):239-242.
[7] 成志勇,万建设,王亚丽,等. PTEN基因对慢性粒细胞白血病Survivin、Xiap、Smac调控的研究.中华医学杂志,2011,91 (40): 2868-2872. Cheng Z Y, Wan J S, Wang Y L. et al. Regulation of wild type PTEN gene on Survivin, Xiap and Smac in chronic leukemia cells. National Medical Journal of China, 2011,91 (40): 2868-2872.
[8] Shen S H, Gu L J, Liu P Q, et al.Comparative proteomic analysis of differentially expressed proteins between K562 and K562/ADM cells. Chin Med J. 2008;121(5):463-468.
[9] Tabellini G, Cappellini A, Tazzari P L,et al. Phosphoinositide 3-kinase/Akt involvement in arsenic trioxide resistance of human leukemia cells. J Cell Physiol. 2005, 202(2):623-634.
[10] Tabellini G, Tazzari P L, Bortul R,et al. Novel 2’-substituted, 3’-deoxy -phosphatidyl-myo-inositol analogues reduce drug resistance in human leukaemia cell lines with an activated phosphoinositide 3-kinase/Akt pathway.Br J Haematol. 2004,126(4):574-582.
[11] Grandage V L, Gale R E, Linch D C,et al. PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-kappaB, Mapkinase and p53 pathways. Leukemia. 2005,19(4):586-594.
[12] Zhou M, Gu L, Findley H W, et al. PTEN reverses MDM2-mediated chemotherapy resistance by interacting with p53 in acute lymphoblastic leukemia cells. Cancer Res. 2003, 63(19):6357-6362.
[13] Liu F, Bardhan K, Yang D, et al. NF-κB directly regulates Fas transcription to modulate Fas-mediated apoptosis and tumor suppression. J Biol Chem. 2012 Jul 20;287(30):25530-25540. Bull Cancer. 2012;99(4):E49-54.
[14] Liu S Y, Liang Q J, Lin T X,et al.Lipopolysaccharide-enhanced early proliferation of insulin secreting NIT-1 cell is associated with nuclear factor-kappaB- mediated inhibition of caspase 3 cleavage. Chin Med J (Engl). 2011;124(22):3652-3656.
[1] CHEN Yu-qiong,TAN Wen-hua,LIU Hai-feng,CHEN Gen. Protective Effect of miR-29a on Lipopolysaccharide-induced Human Pulmonary Microvascular Endothelial Cells Injury by Targeting PTEN Expression[J]. China Biotechnology, 2021, 41(5): 8-16.
[2] DONG Shu-xin,QIN Lei,LI Chun,LI Jun. Transcription Factor Engineering Harnesses Metabolic Networks to Meet Efficient Production in Cell Factories[J]. China Biotechnology, 2021, 41(4): 55-63.
[3] ZHAO Jiu-mei,WANG Zhe,LI Xue-ying. Role of Signal Pathways and Related Factors Regulating Cartilage Formation in Bone Differentiation of Bone Marrow Mesenchymal Stem Cells[J]. China Biotechnology, 2021, 41(10): 62-72.
[4] DAI Qi-nan,ZHANG Jing-hong. Advances in Molecular Mechanisms Related to Tumor Multi-drug Resistance, Autophagy, DNA Repair and Tumor Stem Cells[J]. China Biotechnology, 2020, 40(4): 69-77.
[5] HU Li-jun,DUAN Liang,HUANG Yi-yun,LIN Lu,HUANG Mao,CHEN Lu,PENG Qi,HU Qin,ZHANG Yan,ZHOU Lan. S100A9 Is Involved in Fusobacterium nucleatum-Induced Proliferation and Migration of Colon Cancer HCT116 and SW480 Cells[J]. China Biotechnology, 2020, 40(1-2): 84-91.
[6] Xiao-yong ZHANG,Qian-cheng LUO. Establishment and Clinical Application of LNA-PCR Assay Detecting Hepatitis B Virus Adefovir Dipivoxil Resistance[J]. China Biotechnology, 2018, 38(9): 48-54.
[7] Jun-jie ZHAO,Long ZHANG,Liang WANG,Xu-sheng CHEN,Zhong-gui MAO. Breeding and Physiological Characteristics of ε-Polylysine High-Producing Strain with Double Antibiotic Resistance[J]. China Biotechnology, 2018, 38(8): 59-68.
[8] Wen-ran YUE,Jun-yan YUE,Xiu-juan ZHANG,Qi YANG,Xiao-dong HAN,Rui-gang WANG,Guo-jing LI. The CiNAC1 from Caragana intermedia Promotes Transgenic Arabidopsis Leaf Senescence[J]. China Biotechnology, 2018, 38(4): 24-29.
[9] Jia-wei XU,Hua HE,Jing ZHANG,Chu-chao LEI,Hong CHENG,Yong-zhen HUANG. Research Progress on the Structure and Function of Transcription Factor KLF8 Gene[J]. China Biotechnology, 2018, 38(4): 90-95.
[10] LI Rong-qing,QUAN Chun-shan,ZHANG Li-ying,LIU Jia-lu,ZHANG Xiang,SHANG Fei. Progress in the Synthesis of Artificial Antigen[J]. China Biotechnology, 2018, 38(12): 65-75.
[11] Jia-ao GE,Chang LIU,Jian-gang GONG,Yan-qin LIU. Research Progress of Antibacterial Cyclopeptides[J]. China Biotechnology, 2018, 38(11): 76-83.
[12] LI Ai-fang, GU Yue, LI Xue-ru, SUN Hui, ZHA He, XIE Jia-qing, ZHAO Jia-li, ZHOU Lan. Effects of S100A6 on Proliferation and Migration of Human Cervical Cancer Cells and Its Mechanism[J]. China Biotechnology, 2017, 37(2): 8-14.
[13] SUN Ze-xu, ZHAO Chen, LIAO Jun-yi, WANG Qi, XU Wei, CHEN Cheng, HUANG Wei. Suppression of Runx2 Potentiates BMP2-induced Chondrogenic Differentiation[J]. China Biotechnology, 2016, 36(4): 57-62.
[14] DONG Jian-yi, WANG Xin-xin, WANG Kang-wei, CHEN Jun, LI Hui-ling, WANG Fu-jin, WANG Ai-guo, WANG Jing-yu. MiR-146a/b Expression and Related up and Down-stream Regulatory Mechanisms in Human Hepatoma Cells[J]. China Biotechnology, 2016, 36(12): 8-14.
[15] MA Li, WU Hao, WANG Bin-bin, QIAO Jian-jun, ZHU Hong-ji. Progress in Functions and Regulatory Mechanisms of the Transcription Factor Rex[J]. China Biotechnology, 2016, 36(10): 94-100.