Abstract
Ciclesonide is an FDA-approved glucocorticoid (GC) used to treat asthma and allergic rhinitis. However, its effects on cancer and cancer stem cells (CSCs) are unknown. Our study focuses on investigating the inhibitory effect of ciclesonide on lung cancer and CSCs and its underlying mechanism. In this study, we showed that ciclesonide inhibits the proliferation of lung cancer cells and the growth of CSCs. Similar glucocorticoids, such as dexamethasone and prednisone, do not inhibit CSC formation. We show that ciclesonide is important for CSC formation through the Hedgehog signaling pathway. Ciclesonide reduces the protein levels of GL1, GL2, and Smoothened (SMO), and a small interfering RNA (siRNA) targeting SMO inhibits tumorsphere formation. Additionally, ciclesonide reduces the transcript and protein levels of SOX2, and an siRNA targeting SOX2 inhibits tumorsphere formation. To regulate breast CSC formation, ciclesonide regulates GL1, GL2, SMO, and SOX2. Our results unveil a novel mechanism involving Hedgehog signaling and SOX2 regulated by ciclesonide in lung CSCs, and also open up the possibility of targeting Hedgehog signaling and SOX2 to prevent lung CSC formation.
Highlights
Lung cancer, known as lung carcinoma, is a common cancer and is known to cause uncontrolled cell growth in lung tissue
We showed that ciclesonide effectively suppressed lung cancer cell growth, apoptosis, cell migration, and colony formation
Our observations suggest that ciclesonide reduced SOX2 and Hedgehog signaling, which is important for tumorsphere formation in lung cancer
Summary
Known as lung carcinoma, is a common cancer and is known to cause uncontrolled cell growth in lung tissue. Lung cancer is a major cause of cancer death, accounting for 20% of all cancer-related deaths [1]. Chemotherapy improves survival rate to a limited extent, but the overall survival rate is low due to the recurrence of aggressive tumors [2]. Lung cancer is divided into two groups based on pathological properties. These two types are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for 85% of all lung cancers, and the survival rate is low [3]
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