Epigenetic therapy potential of suberoylanilide hydroxamic acid on invasive human non-small cell lung cancer cells
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Shirong Zhang1,*, Kan Wu2,3,*, Jianguo Feng4,*, Zhibing Wu3, Qinghua Deng3, Chao Guo5, Bing Xia3, Jing Zhang1, Haixiu Huang1, Lucheng Zhu1, Ke Zhang3, Binghui Shen5, Xufeng Chen6, Shenglin Ma1
1Department of Oncology, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, China
2Department of Oncology, Affiliated Hangzhou First People’s Hospital of Zhejiang Chinese Medical University, Hangzhou, China
3Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China
4Cancer Research institute, Zhejiang Cancer Hospital, Hangzhou, China
5Department of Cancer Genetics and Epigenetics, City of Hope National Medical Center, Duarte, CA, USA
6Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA, USA
*These authors have contributed equally to this work
Shenglin Ma, email: [email protected]
Keywords: non-small cell lung cancer, invasion, epigenetics, suberoylanilide hydroxamic acid, epigenetic therapy
Received: March 29, 2016 Accepted: August 24, 2016 Published: September 12, 2016
Metastasis is the reason for most cancer death, and a crucial primary step for cancer metastasis is invasion of the surrounding tissue, which may be initiated by some rare tumor cells that escape the heterogeneous primary tumor. In this study, we isolated invasive subpopulations of cancer cells from human non-small cell lung cancer (NSCLC) H460 and H1299 cell lines, and determined the gene expression profiles and the responses of these invasive cancer cells to treatments of ionizing radiation and chemotherapeutic agents. The subpopulation of highly invasive NSCLC cells showed epigenetic signatures of epithelial-mesenchymal transition, cancer cell stemness, increased DNA damage repair and cell survival signaling. We also investigated the epigenetic therapy potential of suberoylanilide hydroxamic acid (SAHA) on invasive cancer cells, and found that SAHA suppresses cancer cell invasiveness and sensitizes cancer cells to treatments of IR and chemotherapeutic agents. Our results provide guidelines for identification of metastatic predictors and for clinical management of NSCLC. This study also suggests a beneficial clinical potential of SAHA as a chemotherapeutic agent for NSCLC patients.
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