Effect of miR-155 knockdown on the reversal of doxorubicin resistance in human lung cancer A549/dox cells

被引:52
作者
Lv, Lixia [1 ]
An, Xiumei [2 ]
Li, Hongyan [1 ]
Ma, Lanxiu [1 ]
机构
[1] Tianjin Med Univ Canc Inst & Hosp, Tianjin Huanhu Hosp, Dept Clin Lab, Tianjin 300060, Peoples R China
[2] Tianjin Med Univ Canc Inst & Hosp, Biotechnol Immunol Lab, Huanhu Xi Rd, Tianjin 300060, Peoples R China
关键词
microRNA-155; resistance reversal; human lung cancer; S-TRANSFERASE-PI; BREAST-CANCER; MECHANISMS; EXPRESSION; CISPLATIN; APOPTOSIS; PROTEINS; MIRNAS;
D O I
10.3892/ol.2015.3995
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Doxorubicin has been widely used in the treatment of cancer. However, acquired doxorubicin resistance severely hinders the application of the drug. In the present study, doxorubicin resistance was investigated in lung carcinoma. microRNA-155(miR-155) was found to be upregulated in the doxorubicin-resistant A549/dox cell line. Suppression of miR-155 in this cell line considerably reversed doxorubicin resistance, and doxorubicin-induced apoptosis and cell cycle arrest were recovered. Furthermore, reverse transcription-polymerase chain reaction and western blot analysis revealed that miR-155 suppression downregulated the expression of multidrug resistance protein 1, multidrug resistance-associated protein 1, breast cancer resistance protein, glutathione S-transferase-p, Survivin and B-cell lymphoma 2, and upregulated the expression of caspase-3 and caspase-8. In addition, it was found that miR-155 suppression inhibited the activation of AKT and extracellular signal-regulated kinase. The transcriptional activity of nuclear factor-kappa B and activator protein-1 was also downregulated. In summary, the present results indicate that miR-155 may participate in doxorubicin resistance in lung carcinoma. The current study provides a novel target for lung carcinoma treatment.
引用
收藏
页码:1161 / 1166
页数:6
相关论文
共 43 条
[31]   Cancer Statistics, 2014 [J].
Siegel, Rebecca ;
Ma, Jiemin ;
Zou, Zhaohui ;
Jemal, Ahmedin .
CA-A CANCER JOURNAL FOR CLINICIANS, 2014, 64 (01) :9-29
[32]   Oncogenic MicroRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum [J].
Sochor, Marek ;
Basova, Petra ;
Pesta, Michal ;
Dusilkova, Nina ;
Bartos, Jiri ;
Burda, Pavel ;
Pospisil, Vit ;
Stopka, Tomas .
BMC CANCER, 2014, 14
[33]   Mechanisms of resistance to cisplatin and carboplatin [J].
Stewart, David J. .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2007, 63 (01) :12-31
[34]   Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients [J].
Surowiak, P ;
Materna, V ;
Kaplenko, I ;
Spaczynski, M ;
Dietel, M ;
Lage, H ;
Zabel, M .
VIRCHOWS ARCHIV, 2005, 447 (03) :626-633
[35]   MicroRNAs as potential cancer therapeutics [J].
Trang P. ;
Weidhaas J.B. ;
Slack F.J. .
Oncogene, 2008, 27 (Suppl 2) :S52-S57
[36]   Control of translation and mRNA degradation by miRNAs and siRNAs [J].
Valencia-Sanchez, MA ;
Liu, JD ;
Hannon, GJ ;
Parker, R .
GENES & DEVELOPMENT, 2006, 20 (05) :515-524
[37]   Stereotactic radiosurgery for brain metastasis in non-small cell lung cancer [J].
Won, Yong Kyun ;
Lee, Ja Young ;
Kang, Young Nam ;
Jang, Ji Sun ;
Kang, Jin-Hyoung ;
Jung, So-Lyoung ;
Sung, Soo Yoon ;
Jo, In Young ;
Park, Hee Hyun ;
Lee, Dong-Soo ;
Chang, Ji Hyun ;
Lee, Yun Hee ;
Kim, Yeon-Sil .
RADIATION ONCOLOGY JOURNAL, 2015, 33 (03) :207-216
[38]   miR-155*mediates suppressive effect of PTEN 3′-untranslated region on AP-1/NF-κB pathway in HTR-8/SVneo cells [J].
Xue, P. ;
Zheng, M. ;
Diao, Z. ;
Shen, L. ;
Liu, M. ;
Gong, P. ;
Sun, H. ;
Hu, Y. .
PLACENTA, 2013, 34 (08) :650-656
[39]   miR-155 contributes to the progression of glioma by enhancing Wnt/β-catenin pathway [J].
Yan, Zhiyong ;
Che, Shusheng ;
Wang, Jianpeng ;
Jiao, Yingbing ;
Wang, Chao ;
Meng, Qinghai .
TUMOR BIOLOGY, 2015, 36 (07) :5323-5331
[40]   Bcl-2 family proteins and cancer [J].
Yip, K. W. ;
Reed, J. C. .
ONCOGENE, 2008, 27 (50) :6398-6406