|Table of Contents|

Sodium selenite reverses the resistance of lung cancer PC-9/GR cells to gefitinib by increasing ROS and inhibiting PI3K/AKT pathway

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 04
Page:
636-641
Research Field:
Publishing date:

Info

Title:
Sodium selenite reverses the resistance of lung cancer PC-9/GR cells to gefitinib by increasing ROS and inhibiting PI3K/AKT pathway
Author(s):
LI Yanmei; MA Lin; LIU Dan; DENG Shukai
Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Southwest Medical University,Sichuan Luzhou 646000,China.
Keywords:
lung cancer; sodium selenite; reactive oxygen species(ROS); EGFR-TKIs resistance; the PI3K/AKT pathway
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2024.04.008
Abstract:
Objective:To investigate the effects of sodium selenite on the proliferation and apoptosis of lung cancer resistant cells PC-9/GR,and to study whether sodium selenite can improve the resistance to gefitinib and its potential mechanism.Methods:PC-9/GR cells were treated with different concentrations of sodium selenite(0,5,10,20,40 μmol/L) for 24,36,48 hours.The proliferation of PC-9/GR cells was detected by CCK-8 assay,and the appropriate concentration of sodium selenite was selected for subsequent experiments.Cells were treated with different concentrations (0,2.5,5,10,20,40 μmol/L) of gefitinib alone or in combination with sodium selenite (6 μmol/L) for 48 hours.The median inhibitory concentration (IC50) of each time group and the reversal ratio of sodium selenite to PC-9/GR were calculated.Apoptosis was detected by flow cytometry.ROS level was detected by DCFH-DA.The expression levels of p-PI3K,p-AKT,Bax and Bcl-2 were detected by Western blot.Results:With the increase of sodium selenite concentration and the longer treatment time,the cell proliferation inhibition rate increased (P＜0.05).The IC50 of gefitinib alone was 16.051 μmol/L,while in combination with sodium selenite was 5.406 μmol/L.Indicating that sodium selenite could reverse the drug resistance of gefitinib by 2.969 times.Compared with the monotherapy groups,the apoptosis rate of combination group significantly increased.The levels of ROS and the expression of Bax protein were upregulated,while the expression of p-PI3K,p-AKT,and Bcl-2 were downregulated.After eliminating ROS with N-acetylcysteine (NAC),the inhibitory effect of sodium selenite on the PI3K/AKT pathway was counteracted (P＜0.05).Conclusion:Sodium selenite combined with gefitinib can enhance the sensitivity of gefitinib-resistant lung adenocarcinoma cells,inhibit cell proliferation,and induce cell apoptosis.This process may be achieved by downregulating the expression of the PI3K/AKT pathway through ROS-dependent manner.

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