Nitroglycerin Enhances Cisplatin-Induced Cytotoxicity via AKT Inactivation and Thymidylate Synthase Downregulation in Human Lung Cancer Cells
| Autor: | Tzu-Ying Chen, Hsiang-Hung Cheng, Ting-Chuan Yen, Yuan-Cheng Lin, Yun-Wei Lin, Jyh-Cheng Chen, Yong-Cing Taso, Peng-Fang Ma, Jen-Chung Ko |
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| Rok vydání: | 2019 |
| Předmět: |
Lung Neoplasms
Cell Survival Down-Regulation Adenocarcinoma of Lung Antineoplastic Agents Thymidylate synthase Nitroglycerin Downregulation and upregulation Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Humans Lung cancer Cytotoxicity Protein kinase B Pharmacology Cisplatin biology Chemistry Cell growth Drug Synergism Thymidylate Synthase General Medicine Transfection medicine.disease A549 Cells Carcinoma Squamous Cell Cancer research biology.protein Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | Pharmacology. 105:209-224 |
| ISSN: | 1423-0313 0031-7012 |
| Popis: | Nitroglycerin (NTG), a nitric oxide-donating drug, may increase tumor blood flow and consequently increase cancer drug delivery to tumor cells. Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of deoxythymidine monophosphate; we had found that knocking down the expression of TS sensitizes lung cancer cells to cisplatin-induced cytotoxicity. However, whether NTG and cisplatin could induce synergistic cytotoxicity in nonsmall cell lung cancer (NSCLC) cells through modulating TS expression is unknown. In this study, NTG decreased TS expression in an AKT, also known as Protein kinase B (PKB) inactivation dependent manner in human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Enhancement of AKT activity by transfection with constitutive active AKT vectors increased the TS expression level as well as the cell survival pretreated by NTG. Moreover, NTG synergistically enhanced cytotoxicity and cell growth inhibition by cisplatin treatment in NSCLC cells, which were associated with downregulation of TS expression and inactivation of AKT in A549 and H1703 cells. Together, these results may provide a rationale to combine NTG with cisplatin-based chemotherapy to enhance the therapeutic effect for lung cancer in the future. |
| Databáze: | OpenAIRE |
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