Down-regulation of HOTAIR Reverses the Resistance of Gefitinib in HCC827 Cells by Increasing the Expression of PTEN.
10.3779/j.issn.1009-3419.2020.103.13
- Author:
Yang ZHAI
1
;
Qian CHEN
2
;
Yuzhen WANG
1
;
Xu LI
1
;
Lina LI
1
Author Information
1. Department of Oncology, Tumor hospital of Shaanxi Province, Xi'an 710061, China.
2. Department of Reproductive Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, China.
- Publication Type:Journal Article
- Keywords:
Drug resistance;
Gefitinb;
HCC827;
HOTAIR;
PTEN
- From:
Chinese Journal of Lung Cancer
2020;23(9):762-771
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:Lung cancer is the most common cancer worldwide with the highest morbidity and mortality, in which the non-small cell lung cancer accounts for 80% of all cases. The expression of (HOX transcript antisense RNA) HOTAIR were abnormal in a variety of tumor tissues and is involved in the regulation of the occurrence and development of lung cancer. The purpose of this study is to investigate the effect and mechanism of down-regulation of HOTAIR on gefitinib resistance of lung adenocarcinoma HCC827 cells by targeting PTEN.
METHODS:The HOTAIR downstream target gene was predicted by bioinformatics database. The small interfering RNAs (siRNA) which is corresponding to HOTAIR was transfected using Lipofectamine™ 2000. Quantitative real-time PCR (RT-qPCR) and Western blot were used to detect the expression of HOTAIR, PTEN, PI3K and AKT in HCC827 and HCC827GR cells. MTT assay was used to detect the changes in drug resistance of HCC827GR cells. Flow cytometry analysis were used to test the cell proliferation and the rate of apoptosis.
RESULTS:The expression of HOTAIR increased in HCC827GR and the serum of NSCLC patients with gefitinib resistance (P<0.05). Transfection of HOTAIR siRNA decreased the expression of HOTAIR (P<0.05), and increased the expressions of PTEN (P<0.05), while the expression of PI3K and AKT were decreased (P<0.05). Compared with the blank control group, down-regulation of HOTAIR increased the sensitivity of HCC827GR cells to gefitinib. The cell proliferation ability was decreased and the apoptosis was promoted apparently (P<0.05).
CONCLUSIONS:Down-regulation of HOTAIR can suppress the cell growth and promote the apoptosis, and it can reverse the resistance of HCC827GR cells to gefitinib. Its potential mechanism may be related with the targeting of PTEN/PI3K/AKT pathway.
