Epigenetic therapy potential of suberoylanilide hydroxamic acid on invasive human non-small cell lung cancer cells.

Shirong Zhang,Haixiu Huang,Ke Zhang,Shenglin Ma,Chao Guo,Kan Wu,Jianguo Feng,Jing Zhang,Binghui Shen,Qinghua Deng,Bing Xia,Xufeng Chen,Zhibing Wu,Lucheng Zhu

doi:10.18632/oncotarget.11967

Abstract

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.

Highlights

Lung cancer is the most common cancer and the leading cause of cancer death
We further evaluated the potential effects of suberoylanilide hydroxamic acid (SAHA) on the sensitivity of H460 high invasiveness (H-INV) cells to treatments of ionizing radiation (IR) or chemotherapeutic agents, and the results showed that pretreatment with SAHA significantly reduced clonogenic survival of H460 H-INV cells in response to Cisplatin (2 μM), Paclitaxel (10 nM), Docetaxel (0.5 nM) or IR
We showed in this study that invasive cancer cell subpopulations of H460 and H1299 cells show positive molecular signatures for cell invasion, and epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs)

Summary

Introduction

Lung cancer is the most common cancer and the leading cause of cancer death. Tumor aggressiveness in metastatic lesions is the cause of lethality in lung cancer patients, and is responsible for more than 90% of failure for lung cancer treatment [1, 2]. Metastatic potential is a common feature of lung cancer. Lung cancer patients are often diagnosed at late stages, when the cancer has invaded local sites and produced distant metastases [3]. Development of metastasis after initial surgery is a clinical challenge for NSCLC (non-small cell lung cancer) patients with early stage cancers. To improve the clinical management of lung cancer patients, novel strategies for diagnosis at an earlier stages and therapeutic interventions to prevent metastatic spreading of lung cancer are urgently required

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Results

Conclusion