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Epigenetic therapy potential of suberoylanilide hydroxamic acid on invasive human non-small cell lung cancer cells
Shirong Zhang1, Kan Wu2,3, Jianguo Feng4
1Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
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.
Insights
This study identified invasive non-small cell lung cancer (NSCLC) cells with epigenetic changes promoting metastasis. Epigenetic therapy with SAHA reduced invasiveness and improved treatment response in NSCLC models.
Area of Science:
- Oncology
- Cancer Metastasis Research
- Epigenetics
Background:
- Metastasis is the leading cause of cancer mortality.
- Cancer cell invasion is a critical early step in metastasis.
- Identifying mechanisms of invasion is crucial for effective cancer treatment.
Purpose of the Study:
- To isolate and characterize invasive subpopulations of non-small cell lung cancer (NSCLC) cells.
- To investigate the gene expression profiles and treatment responses of invasive NSCLC cells.
- To evaluate the therapeutic potential of suberoylanilide hydroxamic acid (SAHA) in NSCLC.
Main Methods:
- Isolation of invasive cancer cell subpopulations from NSCLC cell lines (H460, H1299).
- Gene expression profiling of invasive subpopulations.
- Assessment of invasive cell responses to ionizing radiation (IR) and chemotherapeutic agents.
- Evaluation of SAHA's effect on invasiveness and treatment sensitization.
Main Results:
- Invasive NSCLC cells exhibited epigenetic signatures of epithelial-mesenchymal transition, stemness, enhanced DNA repair, and cell survival signaling.
- SAHA effectively suppressed cancer cell invasiveness.
- SAHA sensitized cancer cells to IR and chemotherapy.
Conclusions:
- Invasive NSCLC cells possess distinct epigenetic profiles linked to metastatic potential.
- SAHA demonstrates potential as an epigenetic therapy to inhibit NSCLC metastasis.
- SAHA may enhance the efficacy of conventional treatments for NSCLC, suggesting clinical utility.
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