Dexamethasone suppresses the growth of human non-small cell lung cancer via inducing estrogen sulfotransferase and inactivating estrogen
| Autor: | Yin Yuan, Li-jie Wang, Wei Lu, Jian Li, Jingyun Li, Fangran Hao, Tianyan Zhou |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Antineoplastic Agents Hormonal medicine.drug_class Cell Survival Mice Nude Pharmacology Dexamethasone 03 medical and health sciences 0302 clinical medicine Carcinoma Non-Small-Cell Lung Cell Line Tumor polycyclic compounds medicine Animals Humans Pharmacology (medical) Estrogen Sulfotransferase Viability assay Lung Cell Proliferation A549 cell Chemistry Cell growth Estrogen Antagonists Estrogens General Medicine 030104 developmental biology Estrogen Cell culture A549 Cells 030220 oncology & carcinogenesis Female Original Article Sulfotransferases hormones hormone substitutes and hormone antagonists Tamoxifen medicine.drug |
| Zdroj: | Acta pharmacologica Sinica. 37(6) |
| ISSN: | 1745-7254 |
| Popis: | Dexamethasone (DEX) is a widely used synthetic glucocorticoid, which has shown anti-cancer efficacy and anti-estrogenic activity. In this study we explored the possibility that DEX might be used as an endocrine therapeutic agent to treat human non-small cell lung cancer (NSCLC).The viability and proliferation of human NSCLC cell lines A549 and H1299 were assessed in vitro. Anti-tumor action was also evaluated in A549 xenograft nude mice treated with DEX (2 or 4 mg·kg(-1)·d(-1), ig) or the positive control tamoxifen (50 mg·kg(-1)·d(-1), ig) for 32 d. The expression of estrogen sulfotransferase (EST) in tumor cells and tissues was examined. The intratumoral estrogen levels and uterine estrogen responses were measured.DEX displayed mild cytotoxicity to the NSCLC cells (IC50500 μmol/L) compared to tamoxifen (IC5050 μmol/L), but it was able to inhibit the cell proliferation at low micromolar ranges. Furthermore, DEX (0.1-10 μmol/L) dose-dependently up-regulated EST expression in the cells, and inhibited the cell migration in vitro. Triclosan, a sulfation inhibitor, was able to diminish DEX-caused inhibition on the cell viability. In A549 xenograft nude mice, DEX or tamoxifen administration remarkably suppressed the tumor growth. Moreover, DEX administration dose-dependently increased EST expression in tumor tissues, and reduced intratumoral estrogen levels as well as the volumes and weights of uterine.DEX suppresses the growth of A549 xenograft tumors via inducing EST and decreasing estradiol levels in tumor tissues, suggesting that DEX may be used as anti-estrogenic agent for the treatment of NSCLC. |
| Databáze: | OpenAIRE |
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