Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma
| Autor: | Meichao Zhang, Pingting Zhou, Lei Bian, Yanyan Li, Yuan Yao, Ci Xu, Yuanhua Liu, Furao Liu, Dong Li, Bo Li |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Carcinogenesis Mice Nude Antineoplastic Agents Apoptosis Biology Malignancy Autophagy-Related Protein 5 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Autophagy medicine Animals Humans skin and connective tissue diseases neoplasms Molecular Biology Cell Proliferation Mice Inbred BALB C Osteosarcoma Cell Cycle Checkpoints Cell Biology medicine.disease Xenograft Model Antitumor Assays 030104 developmental biology Celecoxib 030220 oncology & carcinogenesis Cancer research Research Paper Developmental Biology medicine.drug |
| Zdroj: | Cell Cycle. 17:997-1006 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.1080/15384101.2018.1467677 |
| Popis: | Osteosarcoma (OS) is the most prevalent bone malignancy in childhood and adolescence, with highly aggressive and early systemic metastases. Here, we reported that celecoxib, a selective COX-2 inhibitor in the NSAID class, exhibits strong antitumor activity in dose dependent manner in two OS cell lines-143B and U2OS. We showed that celecoxib inhibits OS cell growth, causes G0/G1-phase arrest, modulates apoptosis and autophagy and reduces migration in OS cells. In addition, the results of fluorescent mitochondrial probe JC-1 test indicated that the mitochondrial pathway mediates celecoxib-induced apoptosis. Significantly, the autophagy inhibitor CQ combined with celecoxib causes greater cell proliferation inhibition and apoptosis. Pharmacologic inhibition of autophagy with another potent autophagy inhibitor SAR405 also enhances celecoxib-mediated suppression of cell viability. These results were confirmed with shRNAs targeting the autophagy-related gene Atg5. In OS tumor xenografts in vivo, celecoxib also presents antitumor activity. Taken together, our results shed light on the function and mechanism of antitumor action of celecoxib for treatment of OS patients. |
| Databáze: | OpenAIRE |
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