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MDMX is a prognostic factor for non-small cell lung cancer and regulates its sensitivity to cisplatin
- Source :
- Cellular Oncology. 40:357-365
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Chemoradiotherapy is the standard treatment modality for advanced non-small cell lung cancer (NSCLC). However, drug and radiation resistance remain major factors influencing its clinical outcome. The purpose of this study was to evaluate whether MDMX can affect the chemosensitivity and clinical outcome of NSCLC. Quantitative real-time PCR (qRT-PCR) was performed to assess MDMX mRNA expression levels in 105 primary NSCLC tissues, its corresponding non-cancerous tissues and two NSCLC-derived cell lines (A549 and SK-MES-1). In addition, immunohistochemistry was carried out to detect MDMX protein expression in the primary NSCLC tissues. The MDMX expression levels were correlated with clinicopathological and survival features. The effects of MDMX expression knockdown on NSCLC cell proliferation and chemosensitivity were evaluated using MTT, flow cytometry and soft agar colony assays. We found that the mRNA expression level of MDMX in NSCLC tissues was significantly higher than that in its corresponding non-tumorous tissues. High MDMX expression was found to be related to poor tumor cell differentiation, advanced TNM stages and the occurrence of lymph node metastases. Patients with a high MDMX expression level exhibited a lower overall survival rate than those with a low expression level. Multivariate analysis showed that a high MDMX protein expression level may serve as an independent prognostic factor for NSCLC patients. In addition, we found that MDMX expression knockdown combined with cisplatin treatment in vitro significantly increased apoptosis and decreased soft agar colony formation in NSCLC-derived cells. Our data indicate that MDMX expression may serve as an independent unfavorable prognostic factor for NSCLC patient outcome, which in turn may at least partly be due to the ability of the MDMX protein to regulate the proliferative capacity and chemosensitivity of NSCLC cells.
- Subjects :
- Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Lung Neoplasms
MDMX
Antineoplastic Agents
Apoptosis
Kaplan-Meier Estimate
Biology
Flow cytometry
03 medical and health sciences
0302 clinical medicine
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Internal medicine
Biomarkers, Tumor
medicine
Humans
Lung cancer
Cell Proliferation
Cisplatin
Gene knockdown
medicine.diagnostic_test
Cell growth
Proto-Oncogene Proteins c-mdm2
General Medicine
Middle Aged
Prognosis
medicine.disease
respiratory tract diseases
Gene Expression Regulation, Neoplastic
030104 developmental biology
A549 Cells
030220 oncology & carcinogenesis
Molecular Medicine
Immunohistochemistry
Female
RNA Interference
medicine.drug
Subjects
Details
- ISSN :
- 22113436 and 22113428
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Cellular Oncology
- Accession number :
- edsair.doi.dedup.....6fa4aaf5f61e9ba08b63ce050ce64beb