MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway
- 357 Downloads
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.
KeywordsCervical 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
Dulbecco’s modified Eagle’s medium
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.
- 5.Wang CC, Chou HH, Yang LY, Lin H, Liou WS, Tseng CW, et al. A randomized trial comparing concurrent chemoradiotherapy with single-agent cisplatin versus cisplatin plus gemcitabine in patients with advanced cervical cancer: an Asian Gynecologic Oncology Group study. Gynecol Oncol. 2015;137(3):462–7.CrossRefPubMedGoogle Scholar
- 23.Sun Y, St Clair DK, Fang F, Warren GW, Rangnekar VM, Crooks PA, et al. The radiosensitization effect of parthenolide in prostate cancer cells is mediated by nuclear factor-kappaB inhibition and enhanced by the presence of PTEN. Mol Cancer Ther. 2007;6(9):2477–86.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Siddiqa A, Long LM, Li L, Marciniak RA, Kazhdan I. Expression of HER-2 in MCF-7 breast cancer cells modulates anti-apoptotic proteins survivin and Bcl-2 via the extracellular signal-related kinase (ERK) and phosphoinositide-3 kinase (PI3K) signalling pathways. BMC Cancer. 2008. doi: 10.1186/1471-2407-8-129.PubMedPubMedCentralGoogle Scholar