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Psoralen reverses docetaxel-induced multidrug resistance in A549/D16 human lung cancer cells lines
Institution:1. School of Basic Medical Sciences of Southwest Medical University, Luzhou, Sichuan, China;2. College of Life Science, University of the Chinese Academy of Sciences, Beijing, China;3. Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;4. Infinitus Chinese Herbal Immunity Research Centre, Infinitus China Company Ltd, Guangzhou, China
Abstract:Chemotherapy is the recommended treatment for advanced-stage cancers. However, the emergence of multidrug resistance (MDR), the ability of cancer cells to become simultaneously resistant to different drugs, limits the efficacy of chemotherapy. Previous studies have shown that herbal medicine or natural food may be feasible for various cancers as potent chemopreventive drug. This study aims to explore the capablility of reversing the multidrug resistance of docetaxel (DOC)-resistant A549 cells (A549/D16) of psoralen and the underlying mechanisms. In this study, results showed that the cell viability of A549/D16 subline is decreased when treated with psoralen plus DOC, while psoralen has no effect on the cell proliferation on A549 and A549/D16 cells. Furthermore, mRNA and proteins levels of ABCB1 were decreased in the presence of psoralen, while decreased ABCB1 activity was also revealed by flow cytometry. Based on these results, we believe that psoralen may be feasible for reversing the multidrug resistance by inhibiting ABCB1 gene and protein expression. Such inhibition will lead to a decrease in ABCB1 activity and anti-cancer drug efflux, which eventually result in drug resistance reversal and therefore, sensitizing drug-resistant cells to death in combination with chemotherapeutic drugs.
Keywords:Multidrug resistance  P-Glycoprotein  ABCB1  Psoralen  Docetaxel  Lung cancer
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