Han Zhao1, Yu-Zhuo Xie1, Rui Xing1, Ming Sun2, Feng Chi1, Yue-Can Zeng3. 1. Department of Medical Oncology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China. 2. Department of Urology, Shengjing Hospital of China Medical University, Shenyang, 110004, China. 3. Department of Medical Oncology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China. wellyy2005@hotmail.com.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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 NSCLCpatients. 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. CONCLUSIONS: Our data indicate that MDMX expression may serve as an independent unfavorable prognostic factor for NSCLCpatient 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.
Authors: Genglin Jin; Stephen Cook; Bo Cui; William C Chen; Stephen T Keir; Patrick Killela; Chunhui Di; Cathy A Payne; Simon G Gregory; Roger McLendon; Darell D Bigner; Hai Yan Journal: Neuro Oncol Date: 2010-05-14 Impact factor: 12.300
Authors: A Shvarts; W T Steegenga; N Riteco; T van Laar; P Dekker; M Bazuine; R C van Ham; W van der Houven van Oordt; G Hateboer; A J van der Eb; A G Jochemsen Journal: EMBO J Date: 1996-10-01 Impact factor: 11.598
Authors: Xin Han; Guillermo Garcia-Manero; Timothy J McDonnell; Guillermina Lozano; L Jeffrey Medeiros; Lianchun Xiao; Gary Rosner; Martin Nguyen; Michael Fernandez; Yasmine A Valentin-Vega; Juan Barboza; Daniel M Jones; Georgios Z Rassidakis; Hagop M Kantarjian; Carlos E Bueso-Ramos Journal: Mod Pathol Date: 2006-11-24 Impact factor: 7.842
Authors: Tong Sun; Gwo-Shu Mary Lee; William K Oh; Mark Pomerantz; Ming Yang; Wanling Xie; Matthew L Freedman; Philip W Kantoff Journal: Clin Cancer Res Date: 2010-09-20 Impact factor: 12.531
Authors: Qiong Yu; Yan Li; Kun Mu; Zhishuang Li; Qingyong Meng; Xiaojuan Wu; Yan Wang; Li Li Journal: Diagn Pathol Date: 2014-03-25 Impact factor: 2.644