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J. Feng
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P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.03-012 - Combined Effects of SAHA and Cisplatin on Radiation Sensitivity and Cancer Cell Invasion in NSCLC (ID 538)
09:30 - 09:30 | Author(s): J. Feng
- Abstract
Background:
Lung cancer is a leading cause of cancer mortality worldwide. In an effort to improve local control of the disease and to increase survival, concurrent chemoradiotherapy has been explored as a therapeutic option. Of them, cisplatin-based chemoradiotherapy is currently used as first line therapy for non-small-cell lung cancer (NSCLC). However, the chemotherapeutic agents cannot be administered for most patients at full doses safely with radical doses of thoracic radiation, and thus further optimizations of chemotherapy regimen to be given with radiation are needed.
Methods:
We examined the effects of suberoylanilide hydroxamic acid (SAHA) and cisplatin on DNA damage repairs using U2OS reporter cells and in vivo end-joining assay, and determined the combination effects of SAHA and cisplatin on various cell lines, primary tumor tissues and in vivo xenograft in response to irradiation. We also investigated the potential differentiation effect of SAHA and its consequent effect on cancer cell invasion in cisplatin-treated cancer cells.
Results:
Our data demonstrated that SAHA and cisplatin compromised distinct DNA damage repair pathways. Treatment with SAHA enhanced synergistic radiosensitization effects of cisplatin in NSCLC cells, and induced prolonged persistence of γ-H2A.X nuclear foci in irradiated primary NSCLC tumor tissues treated with cisplatin. SAHA combined with cisplatin also significantly increased inhibitory effect of ionizing radiation on tumor growth in mouse xenograft model. In addition, we showed here that SAHA could induce differentiation in stem cell-like cancer cell population, reduce tumorogenesity and decrease the invasion/migration capabilities of human lung cancer H460 cells.
Conclusion:
Our results suggest a potential clinical impact for SAHA as a radiosensitizer and as a part of chemoradiotherapy regimen for NSCLC. The strategy may also benefit those patients with high risk of cancer metastasis.
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-053 - Characterization of Invasive Cancer Cells and Potential Therapeutic Effect of Suberoylanilide Hydroxamic Acid on Human Lung Cancer Metastasis (ID 223)
09:30 - 09:30 | Author(s): J. Feng
- Abstract
Background:
Lung cancer is a worldwide problem andthe leading cause of death among all malignancies. Despite tremendous progresses in diagnosis and treatment, the overall treatment outcomes for lung cancer patients remain poor, and metastatic lung cancer is responsible for more than ninety percent of lung cancer related deaths. However, the details for lung cancer invasion and thereafter metastasis remain unclear. In this study, we characterized the biological features of invasive human lung cancer cells, and investigated the potential therapeutic effects of Suberoylanilide Hydroxamic Acid (SAHA) on invasive cancer cell subpopulation.
Methods:
Boyden-type cell invasion chambers were used for isolation of cancer cell subpopulations with high invasiveness (H-INV) and low invasiveness (L-INV) from human lung cancer H460 cells. The potential enrichment of stem cell-like cancer cells in H-INV cells and the resistances of H-INV cells to chemotherapy and radiation treatment were investigated. We also tested the effects of SAHA on the differentiation of cancer stem cell and its consequences on cancer cell invasion and the sensitivities to radio/chemotherapies in H-INV cells. Furthermore, microarray for message RNA was performed for identification of gene expression profiling for invasive cancer cells.
Results:
Comparing to L-INV cells, H-INV cells are with enrichments of stem cell-like cancer cells, with increased positive staining of putative stem cell markers such as CD24[low]/CD44[+] and OCT3/4, and more tumorigenic. H-INV cells are also more resistant to treatments of chemotherapeutic agents and ionizing radiation. Treatment with SAHA can induce differentiation of stem cell-like cell in H-INV cells, causing reduced cancer cell invasion and increased sensitivity to chemo/radiotherapy in cells. With mRNA microarray assay, we identified 453 genes differentially expressed in H-INV versus L-INV, and five of these genes have been further tested for their significances in paired primary and metastatic lung tumors.
Conclusion:
Our study suggested putative roles of cancer stem cell in lung cancer invasion and migration. Study also showed that invasive lung cancer cells are resistant to most of first-line and second-line chemotherapeutic agents and radiotherapy, indicating novel therapeutic strategies are needed for the treatment of metastatic lung cancer. Of this setting, SAHA may serve as a chemotherapeutic agent for benefiting lung cancer patients. The candidate genes identified in this study may also have clinic impact as potential metastatic predictors for diagnosis and prognosis for human lung cancer.
