p53 sensitizes chemoresistant non-small cell lung cancer via elevation of reactive oxygen species and suppression of EGFR/PI3K/AKT signaling

Cancer Cell International
Yize ZhangElaine Lai-Han Leung

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths primarily due to chemoresistance. Somatic mutation of TP53 (36%) and epidermal growth factor receptor (EGFR; > 30%) are major contributors to cisplatin (CDDP) resistance. Substantial evidence suggests the elevated levels of reactive oxygen species (ROS) is a key determinant in cancer. The elevated ROS can affect the cellular responses to chemotherapeutic treatments. Although the role of EGFR in PI3K/Akt signaling cascade in NSCLC is extensively studied, the molecular link between EGFR and p53 and the role of ROS in pathogenesis of NSCLC are limitedly addressed. In this study, we investigated the role of p53 in regulation of ROS production and EGFR signaling, and the chemosensitivity of NSCLC. In multiple NSCLC cell lines with varied p53 and EGFR status, we compared and examined the protein contents involved in EGFR-Akt-P53 signaling loop (EGFR, P-EGFR, Akt, P-Akt, p53, P-p53) by Western blot. Apoptosis was determined based on nuclear morphological assessment using Hoechst 33258 staining. Cellular ROS levels were measured by dichlorofluorescin diacetate (DCFDA) staining followed by flow cytometry analysis. We have demonstrated for the first time that activa...Continue Reading

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Citations

Mar 5, 2021·Molecular Biology Reports·Zongyu LiuKai Zhang
Mar 28, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Hardyanti Eka PutriPithi Chanvorachote
May 15, 2020·Combinatorial Chemistry & High Throughput Screening·Pradeep HanumanthappaAparna H Sosalegowda
Jul 3, 2021·International Journal of Molecular Sciences·Sadaf DorandishHedeel Guy Evans
Aug 28, 2021·International Journal of Molecular Sciences·Jolanta KryczkaEwa Brzeziańska-Lasota

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Methods Mentioned

BETA
ubiquitination
protein assay
electrophoresis
flow cytometry
xenograft

Software Mentioned

Graph Pad Prism
FlowJo

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