Moter activity; overexpression of EZH2 resisted the AZD3759 site PPI-inhibited cell growth, and
Moter activity; overexpression of EZH2 resisted the PPI-inhibited cell growth, and intriguingly, negative feedback regulation of SAPK/JNK signaling. Finally, exogenous expression of DNMT1 antagonized the PPIsuppressed EZH2 protein expression. Consistent with this, PPI inhibited tumor growth, protein expression levels of p65, DNMT1 and EZH2, and increased phosphorylation of SAPK/JNK in vivo. Conclusion: Our results show that PPI inhibits growth of NSCLC cells through SAPK/JNK-mediated inhibition of p65 and DNMT1 protein levels, subsequently; this results in the reduction of EZH2 gene expression. The interactions among p65, DNMT1 and EZH2, and feedback regulation of SAPK/JNK by EZH2 converge on the overall responses of PPI. This study reveals a novel mechanism for regulating EZH2 gene in response to PPI and suggests a new strategy for NSCLC associated therapy. Keywords: PPI, NSCLC, SAPK/JNK, NF-kB/p65, EZH2, DNMT* Correspondence: [email protected]; [email protected] 2 Department of Medical Oncology, Guangdong Provincial Hospital PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28549975 of Chinese Medicine, The Second Clinical Medical Collage, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China 1 Laboratory of Tumor Molecular Biology and Targeted Therapies of TCM, Guangdong Provincial Hospital of Chinese Medicine, No. 111, Dade Road, Guangzhou, Guangdong Province 510120, China?2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Li et al. Journal of Experimental Clinical Cancer Research (2016) 35:Page 2 ofBackground Lung cancer is the most common type of malignancy worldwide, and the leading cancer-related cause of death of both men and women. The majority of lung cancers are the non-small cell lung cancer (NSCLC) presented with advanced stage [1]. Despite recent advances in clinical and experimental studies in the treatment of lung cancer, the prognosis still remains poor due to the uncountable recurrence and metastasis [1, 2]. Therefore, there is an urgent need to search new agents with minimal side effects and improved treatment efficacy. These included components from Chinese medical herbal plants; among those, polyphyllin I (PPI) may be one of such candidates. PPI, a bioactive phytochemical extracted from the Rhizoma of Paris polyphylla, has been reported to possess preclinical anticancer efficacy in various cancer types [3?]. PPI induced apoptosis and reversed epithelial mesenchymal transition in human osteosarcoma cells [7]. Also, PPI triggered cell apoptosis, and inhibited cell growth via regulating caspase activation pathway, increasing c-Jun expression and reducing differential gene, such as phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta (PIK3C2) and wingless-type MMTV integration site family member 5A (Wnt5A), expressions in human ovarian cancer cells [5]. Moreover, one study showed that PPI exhibited anti-tumor effect in NSCLC cells in vitro and in vivo at least through.
