Interferon-α and cyclooxygenase-2 inhibitor cooperatively mediates TRAIL-induced apoptosis in hepatocellular carcinoma
| Autor: | Qinglong Li, Darong Yang, Nianli Liu, Chen Liu, Qunfeng Wu, Xiaoxin Qiu, Xiaohong Wang, Hanguo Dan, Man Xia, Haizhen Zhu, Chaohui Zuo, Michael J. Burns, Jingshi Liu, Hailong Xie |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Programmed cell death Carcinoma Hepatocellular Hepatocellular carcinoma HLCZ01 Mice Nude Antineoplastic Agents Apoptosis Pharmacology Tumor necrosis factor-related apoptosis-inducing ligand TNF-Related Apoptosis-Inducing Ligand Nude mouse Interferon Cell Line Tumor medicine Animals Humans Cyclooxygenase-2 Combination therapy neoplasms Mice Inbred BALB C Sulfonamides Cyclooxygenase 2 Inhibitors biology Cell growth Liver Neoplasms Interferon-alpha Drug Synergism Cell Biology biology.organism_classification medicine.disease Xenograft Model Antitumor Assays digestive system diseases Celecoxib Caspases biology.protein Pyrazoles Cyclooxygenase medicine.drug |
| Zdroj: | Experimental Cell Research. 333:316-326 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2015.02.013 |
| Popis: | Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Interferon-alpha (IFN-α) has recently been recognized to harbor therapeutic potential in the prevention and treatment of HCC, but it remains controversial as to whether IFN-α exerts direct cytotoxicity against HCC. Cyclooxygenase-2 (COX-2) is overexpressed in HCC and is considered to play a role in hepatocarcinogenesis. Therefore, we aimed to elucidate the combined effect of a COX-2 inhibitor, celecoxib, and IFN-α on in vitro growth suppression of HCC using the hepatoma cell line HLCZ01 and the in vivo nude mouse xenotransplantation model using HLCZ01 cells. Treatment with celecoxib and IFN-α synergistically inhibited cell proliferation in a dose- and time-dependent manner. Apoptosis was identified by 4׳,6-diamidino-2-phenylindole dihydrochloride and fluorescent staining. IFN-α upregulated the expression of TRAIL, while celecoxib increased the expression of TRAIL receptors. The combined regimen with celecoxib and IFN-α reduced the growth of xenotransplanted HCCs in nude mice. The regulation of IFN-α- and COX-2 inhibitor-induced cell death is impaired in a subset of TRAIL-resistant cells. The molecular mechanisms of HCC cells resistant to TRAIL-induced apoptosis were explored using molecular biological and immunological methods. Interferon-α and the COX-2 inhibitor celecoxib synergistically increased TRAIL-induced apoptosis in hepatocellular carcinoma. These data suggest that IFN-α and celecoxib may offer a novel role with important implications in designing new therapeutics for TRAIL-resistant tumors. |
| Databáze: | OpenAIRE |
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