High frequency of double drug resistance in the B16 melanoma cell line |
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| Affiliation: | 1. Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States;2. Department of Civil and Environmental Engineering, Northeastern University, Boston, MA 02115, United States;3. Department of Urban Studies and Planning, Massachusetts Institute of Technology, Cambridge, MA 02139, United States;1. School of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, PR China;2. School of Environmental Engineering, Henan University of Technology, Zhengzhou, Henan 450001, PR China;3. School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou, Henan 450001, PR China;4. College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, PR China;1. Research Center of Pharmaceutical Preparations and Nanomedicine, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China;2. Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;3. Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;4. Chongqing Key Laboratory for Pharmaceutical Metabolism Research, College of 10 Pharmacy, Chongqing Medical University, Chongqing 400016, China;5. Pharmaceutical Engineering Research Center, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China;1. Duke Fertility Center, Duke University, Durham, North Carolina;2. Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina |
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| Abstract: | Methotrexate (MTX) and N-(phosphonacetyl)-l-aspartate (PALA) are two agents to which cellular resistance can be conferred by gene amplification, but they do not generally show cross resistance. However, combined treatment with these two agents produced drug resistant cells in the B16 melanoma cell line at a much higher frequency than would be expected if resistance to the two agents was totally independent. An isolated doubly resistant clone, B16-F1 MP, showed a high frequency of resistance to pyrazofurin and ouabain, which are also agents to which resistance can be conferred by gene amplification. Thus MTX combined with PALA selected cells with an ‘amplificator’ phenotype (an increased ability to amplify parts of the genome). These B16-F1 MP cells had a decreased ability to form experimental lung metastases compared with the parent line but this difference was not found in baby hamster kidney cells with the amplificator phenotype. The mechanism underlying drug resistance may need to be considered when designing combination chemotherapy. |
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