In-vitro and in-vivo inhibition of melanoma growth and metastasis by the drug combination of celecoxib and dacarbazine
| Autor: | Xiangming Guan, Satya S. Sadhu, Shenggang Wang, Yang Yang, Teresa Seefeldt, Ranjith Kumar Averineni |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug Cancer Research Skin Neoplasms Dacarbazine media_common.quotation_subject Dermatology Metastasis 03 medical and health sciences Mice 0302 clinical medicine In vivo medicine Animals Humans Neoplasm Metastasis neoplasms Melanoma media_common Cell Proliferation Cancer prevention Cyclooxygenase 2 Inhibitors Cell growth business.industry medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Oncology Celecoxib 030220 oncology & carcinogenesis Cancer research Female business medicine.drug |
| Zdroj: | Melanoma research. 26(6) |
| ISSN: | 1473-5636 |
| Popis: | Celecoxib has been found to be effective in cancer prevention and treatment. Its combination with other chemotherapeutic agents was reported to produce synergistic/additive effects on various cancers. Dacarbazine (DTIC) is one of the most commonly used drugs in the treatment of metastatic melanoma. This investigation aimed to determine the in-vitro and in-vivo effects of the drug combination of celecoxib and DTIC on melanoma growth and metastasis. Melanoma cells B16-F10 and SK-MEL-28, and female C57BL/6 mice were used for the study. Our in-vitro data showed that significant synergistic effects were obtained when celecoxib was used together with various concentrations of DTIC. A study with B16-F10 cells using flow cytometry analysis showed that the drug combination induced significantly more apoptosis than each drug used individually. Our in-vivo results showed that the drug combination was much more effective than each drug used alone for the inhibition of both melanoma growth and metastasis in the B16-F10+C57BL/6 mouse models. For melanoma growth, the median survival rates for phosphate-buffered saline (PBS) (control), celecoxib (30 mg/kg), DTIC-1 (10 mg/kg), DTIC-2 (positive control, 50 mg/kg), and the drug combination (DTIC 10 mg/kg+celecoxib 30 mg/kg) were 6, 6.5, 7.5, 7.5, and 9 days, respectively. For melanoma metastasis, the average number of metastatic tumors in murine lungs was 53.7±10.7, 31.8±18.6, 21.2±21.7, 7.0±9.0, and 0.8±2.0 for PBS, DTIC-1, celecoxib, the drug combination, and DTIC-2. Our results warrant further investigation of the combination as an effective treatment for melanoma patients. |
| Databáze: | OpenAIRE |
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