Abstract
Drug resistance is an obstacle to chemotherapy in non-small cell lung cancer caner (NSCLC). It has been reported cancer stem cells are regarded as the mediators of drug resistance, metastasis, and/or recurrence. Sphere-forming cells isolated from cancer cell lines are identified as cancer stem cells and broadly utilized for cancer stem cell studies. In this study, sphere-forming cells were isolated from NCI-H460 (H460) cells, the NSCLC cell line. The H460 spheres demonstrated increased invasion capacity as compared with H460 adherent cells and also appeared to be resistant to doxorubicin and cisplatin which are chemotherapy drugs. The mechanism involves in part through Notch signaling and Slug, known as a direct target of Notch1. The expression of Notch1 and Slug was remarkably higher in H460 spheres compared to H460 adherent cells. In addition, suppression of Notch1 expression, accompanied by decreased Slug expression, reversed the increased invasion capacity and the acquired drug resistance in H460 spheres. These findings suggest that Notch1 is a potential therapeutic target for cancer stem cells as a strategy for resolving metastasis and resistance to anticancer drugs.
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