Characterization of anti-psychotic agents as lung cancer stem cell inhibitors
| Autor: | Po-Wei Huang, 黃柏維 |
|---|---|
| Rok vydání: | 2017 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 105 Lung cancer is the leading cause of cancer death around the world. There are two major types of lung cancer: small cell lung cancer and non-small cell lung cancer (NSCLC). Cisplatin plus gemcitabine are used to treat to squamous lung cancer; cisplatin plus pemetrexed (Alimta) are used to treat lung adenocarcinoma. After the front-line treatment, most NSCLC patients develop to drug resistant to chemotherapy due to the existence of cancer stem cells (CSCs). Therefore, to reduce the drug resistance and to find potential drugs to eradicate CSCs are important strategy to treat cancer patients. From connectivity map, our laboratory found that phenothiazine derivatives had potential to reverse CSCs gene expression signatures. Through this project, we repurposed prochlorperazine and thioridazine to combine with chemotherapeutic agents to kill cancer stem cells and parental cells. In previous study, prochlorperazine could inhibit lung cancer sphere cells and decreased CSC markers and induced apoptosis in lung cancer sphere cells. But the mechanism of prochlorperazine was still unclear. Here, we used the gene signatures of prochlorperazine and thioridazine via L1000 microarray to query CPDB and LINCS database, and found prochlorperazine could down-regulate VEGF signal pathway. Biochemical data also supported this prcdiction. In conclusion, prochlorperazine treatment, it can decrease VEGF-A and IL-6 secretions were reduced, representing the inhibition of angiogenesis and tumorigenesis factor. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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