Tumor Biology

, Volume 37, Issue 3, pp 3939–3947 | Cite as

MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway

  • Juan Du
  • LiNa Wang
  • ChenXi Li
  • HuiLun Yang
  • YuanBo Li
  • Haiyang Hu
  • Hui Li
  • ZongFeng Zhang
Original Article


Patients with cervical cancer show minimal clinical response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). The molecular mechanisms underlying sensitivity to gefitinib are unknown. The purpose of this study was to investigate the possible mechanism by which microRNA-221 (miR-221) affects sensitivity to gefitinib. We showed that miR-221 expression was significantly increased in cervical cancer tissues compared with adjacent normal tissues. Upregulation of miR-221 expression in cervical cancer cells decreased PTEN expression levels, resulting in increased pAkt and BCL-2 expression. Importantly, gefitinib sensitivity was decreased by the upregulation of miR-221, which was blocked by pcDNA-PTEN co-transfection or by the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002. These data suggest that miR-221 can reduce the sensitivity of cervical cancer cells to gefitinib through the PTEN/PI3K/Akt signaling pathway. miR-221 represents a potential target to increase the sensitivity to gefitinib in cervical cancer treatment.


Cervical cancer miR-221 Gefitinib PTEN 



National Comprehensive Cancer Network


Tyrosine kinase inhibitors


Non-small-cell lung cancers


Epidermal growth factor receptor




Phosphatase and tensin homolog deleted on chromosome ten


Phosphatidylinositol-3 kinase


Dulbecco’s modified Eagle’s medium


Dimethyl sulfoxide


Matrix metalloproteinase 2


Mitogen-activated protein kinase


Hepatocyte growth factor



This work was supported by a foundation of the Heilongjiang Provincial Educational Department, China (Grant No. 11551163).

Compliance with ethical standards

Written informed consent was obtained from the patients prior to participation in this study.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Juan Du
    • 1
  • LiNa Wang
    • 1
  • ChenXi Li
    • 1
  • HuiLun Yang
    • 1
  • YuanBo Li
    • 1
  • Haiyang Hu
    • 1
  • Hui Li
    • 1
  • ZongFeng Zhang
    • 1
  1. 1.Department of Obstetrics and Gynecology, Second Affiliated HospitalHarbin Medical UniversityHarbinChina

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