Cisplatin sensitivity mediated by NKX2-1 in lung adenocarcinoma is dependent on p53 mutational status via modulating TNFSF10 expression

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24781

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24781

Title:	Cisplatin sensitivity mediated by NKX2-1 in lung adenocarcinoma is dependent on p53 mutational status via modulating TNFSF10 expression
Authors:	Chen, MJ;Chen, PM;Wang, L;Shen, CJ;Chen, CY;Lee, H
Keywords:	NKX2-1;TNFSF10;cisplatin;p53 mutational status;lung adenocarcinoma
Date:	2020
Issue Date:	2022-08-09T08:07:54Z (UTC)
Publisher:	E-CENTURY PUBLISHING CORP
ISSN:	2156-6976
Abstract:	NKX2-1 was shown to enhance cisplatin sensitivity in KRAS-mutated cells, but it conferred cisplatin resistance in EGFR-mutated lung adenocarcinoma cells. However, NKX2-1 as a dual role in tumor progression depended on p53 mutational status via modulation of the NF-kappa B pathway. We hypothesized that NKX2-1 may confer cisplatin resistance in p53-mutated (p53-MT) lung adenocarcinoma cells but may enhance cisplatin sensitivity in wild-type (p53-WT) cells. In the present study, six p53-MT and -p53-WT cell lines were treated with various concentrations of cisplatin to calculate the inhibitory concentration of cisplatin for 50% cell viability (IC50). The IC50 value was positively correlated with NKX2-1 expression in the p53-MT cells but negatively correlated in the p53-WT cells. TNFSF10 was identified in a microarray analysis as a potential candidate responsible for NKX2-1-mediated apoptosis induced by cisplatin. The retrospective study evaluated 97 surgically resected lung adenocarcinoma patients receiving cisplatinbased chemotherapy to explore the possible association between NKX2-1 expression and tumor response. Patients with higher TNFSF10 mRNA levels, as determined by real-time reverse transcription-polymerase Chain Reaction (RT-PCR), typically showed an favorable response when compared with patients with lower TNFSF10 mRNA levels. Additionally, the association of higher TNFSF10 mRNA levels with favorable response was only revealed in p53-WT patients, not in p53-MT patients. Higher NKX2-1 mRNA levels were associated with an unfavorable response in patients with p53-MT tumors but a favorable response in patients with p53-WT tumors. In summary, modulation of TNFSF10 expression by NKX2-1 may be a potential indicator for predicting the response to cisplatin-based chemotherapy in patients with lung adenocarcinomas.
URI:	https://www.webofscience.com/wos/woscc/full-record/WOS:000528167100014 https://ir.csmu.edu.tw:8080/handle/310902500/24781
Relation:	AMERICAN JOURNAL OF CANCER RESEARCH ,2020 ,v10 ,issue 4 ,p1229-1237
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

Files in This Item:

There are no files associated with this item.

Loading...