P-糖蛋白过表达与人骨肉瘤顺铂耐药相关。
P-Glycoprotein Overexpression Is Associated With Cisplatin Resistance in Human Osteosarcoma.
作者信息
He Chao, Sun Zhenyu, Hoffman Robert M, Yang Zhijian, Jiang Yuhang, Wang Lei, Hao Yongqiang
机构信息
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
AntiCancer, Inc., San Diego, CA, U.S.A.
出版信息
Anticancer Res. 2019 Apr;39(4):1711-1718. doi: 10.21873/anticanres.13277.
BACKGROUND/AIM: Osteosarcoma (OS) is a diagnosed primary cancer of the bone. Despite the great advances that have been made during the past decades in OS therapy, drug resistance and tumor recurrence are still major problems. It is urgent to find novel strategies to overcome drug resistance in order to prolong the survival time of OS patients.
MATERIALS AND METHODS
Cell viability was investigated by the cell count kit-8 (CCK-8) and colony formation assays. P-Glycoprotein (P-gp) expression was analyzed by RT-qPCR and western blot. A xenograft mouse model was used to identify the synergistic efficacy of a P-gp inhibitor with cisplatin. Student's t-test was used to determine statistically significant differences.
RESULTS
P-gp expression levels were associated with cisplatin efficacy in OS patients. OS cells with higher P-gp expression were more resistant to cisplatin. Knockdown or inhibition of P-gp sensitized OS cells to cisplatin.
CONCLUSION
Down-regulating the expression of P-gp in OS maybe a promising strategy to overcome cisplatin resistance.
背景/目的：骨肉瘤（OS）是一种已确诊的原发性骨癌。尽管在过去几十年中骨肉瘤治疗取得了巨大进展，但耐药性和肿瘤复发仍然是主要问题。迫切需要找到克服耐药性的新策略，以延长骨肉瘤患者的生存时间。
材料与方法
通过细胞计数试剂盒-8（CCK-8）和集落形成试验研究细胞活力。通过RT-qPCR和蛋白质免疫印迹分析P-糖蛋白（P-gp）表达。使用异种移植小鼠模型确定P-gp抑制剂与顺铂的协同疗效。采用学生t检验确定统计学上的显著差异。
结果
P-gp表达水平与骨肉瘤患者的顺铂疗效相关。P-gp表达较高的骨肉瘤细胞对顺铂更耐药。敲低或抑制P-gp可使骨肉瘤细胞对顺铂敏感。
结论
下调骨肉瘤中P-gp的表达可能是克服顺铂耐药的一种有前景的策略。
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