206P - Hypoxia-Induced Cell Stemness Leads to Drug Resistance and Poor Prognosis in Lung Adenocarcinoma

Abstract

ABSTRACT Aim: We aimed to prove that hypoxia may lead to an increasing number of cancer stem cells or cancer cell stemness. Therefore, targeting of a stem-like cell population, especially CD166-positive cells, may represent a novel therapeutic strategy to treat lung cancer. Methods: We used cobalt dichloride (CoCl2) to create a hypoxic environment for the lung adenocarcinoma cell line A549 and its cisplatin-resistant cell line A549/DDP. The change in cell stemness was detected by quantitative real-time PCR and drug resistance was measured by determining the IC50 value. The cancer stem-like cell population of the cell-line was detected by flowcytometry and separated by magnetic antibodies which recognized the cancer stemness marker CD166. A cultured stem-like cell population was compared with other cells not expressing the stem cell marker using proliferation assay and IC50 values. Finally, a tissue array was used to analyze the relationship between hypoxia-induced stemness and overall survival after radical surgery. Results: Chemical-induced hypoxia changed cell stemness by enhancing stem cell transcription factors and markers of chemotherapeutic drug resistance, such as cisplatin, docetaxel and pemetrexed. The CD166-positive cancer stem cell-like population showed greater drug resistance compared to CD166-negativecells. Tissue array also showed poorer prognosis for patients whose tissues expressed higher levels of CD166. Conclusions: Our findings indicate that chemical hypoxia may augment cancer cell stemness and drug resistance in CD166-positive stem cells. Moreover, CD166 expression may be a key marker in the monitoring and clinical management of multiple cancer therapies. Disclosure: All authors have declared no conflicts of interest.