Li Changlong, Wu Hezhen, Yang Yanfang, Liu Jianwen, Chen Zhenwen
School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China.
School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P.R. China.
Oncol Lett. 2018 Jun;15(6):9673-9680. doi: 10.3892/ol.2018.8592. Epub 2018 Apr 27.
Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy efficacy. In the present study, 6-O-angeloylplenolin repressed the overexpression of ATP binding cassette subfamily B member 1 () and increasing the intracellular concentration of anticancer drugs. A reduction in P-glycoprotein expression (encoded by ) was observed in parallel with a decline in mRNA expression in vincristine-resistant HCT (HCT-8/VCR) cells treated with 6-O-angeloylplenolin. In addition, 6-O-angeloylplenolin suppressed the activity of the gene promoter. Treatment with 6-O-angeloylplenolin also decreased the amount of the specific protein complex that interacted with the gene promoter in HCT-8/VCR cells, potentially leading to the suppression of expression. Treatment with 6-O-angeloylplenolin inhibited the nuclear translocation of Y-box binding protein-1 in HCT-8/VCR cells treated with 6-O-angeloylplenolin, contributing to the negative regulation of . Finally, 6-O-angeloylplenolin reversed VCR resistance in an HCT/VCR xenograft model. In conclusion, 6-O-angeloylplenolin exhibited a MDR-reversing effect by downregulating expression and could represent a novel adjuvant agent for chemotherapy.
多药耐药性（MDR）是癌症化疗疗效的主要障碍。在本研究中，6-O-当归酰苦艾素抑制了ATP结合盒亚家族B成员1（）的过表达，并提高了抗癌药物的细胞内浓度。在用6-O-当归酰苦艾素处理的长春新碱耐药HCT（HCT-8/VCR）细胞中，观察到P-糖蛋白表达（由编码）的降低与mRNA表达的下降同时出现。此外，6-O-当归酰苦艾素抑制了基因启动子的活性。用6-O-当归酰苦艾素处理还减少了HCT-8/VCR细胞中与基因启动子相互作用的特异性蛋白复合物的量，这可能导致表达的抑制。用6-O-当归酰苦艾素处理抑制了用6-O-当归酰苦艾素处理的HCT-8/VCR细胞中Y盒结合蛋白-1的核转位，从而对产生负调控作用。最后，6-O-当归酰苦艾素在HCT/VCR异种移植模型中逆转了长春新碱耐药性。总之，6-O-当归酰苦艾素通过下调表达表现出多药耐药逆转作用，可能成为一种新型的化疗辅助药物。
