PARP抑制剂新型生物标志物的初步研究
Preliminary study on a novel biomarker of PARP inhibitors
目的:寻找新的能与ADP核糖聚合酶(Poly ADP-ribose polymerase,PARP)形成合成致死效应的基因,提出PARP抑制剂新型标记物。方法:利用siRNA和PNKP (polynucleotide kinase/phosphatase) 抑制剂PP23干扰SW480细胞中PNKP蛋白的表达和功能,检测PNKP蛋白被干扰后PARP抑制剂奥拉帕尼对SW480细胞抑制的影响。分别将不同浓度的PARP抑制剂奥拉帕尼作用于PNKP蛋白干扰前后的SW480细胞,用MTT法检测两组细胞的增值活力,Western blot检测siRNA干扰后的SW480细胞中PNKP蛋白的表达。结果:siRNA降低SW480细胞中PNKP蛋白的表达及PNKP抑制剂PP23抑制PNKP蛋白的功能都显著增强了细胞对奥拉帕尼的敏感性。结论:降低PNKP蛋白的表达和干扰PNKP蛋白的功能都会增强SW480细胞对奥拉帕尼的敏感性,其结果提示了SW480对PARP抑制剂的敏感性可能与PNKP蛋白有关。
iscovery of a novel gene which can form a lethal effect with ADP-ribose polymerase (PARP). Method: siRNA and PNKP inhibitor PP23 were used to interfere in the expression and function of PNKP protein in SW480 cells. The anti-proliferation activity of Olaparib, PARP inhibitor, was detected after the interference of siRNA and PP23. Wild and PNKP-disturbed SW480 cells were treated with different concentrations of Olaparib, respectively. MTT assay was performed to detect the viability of the two groups of cells. Western blot was implemented to detect the expression of PNKP protein in SW480 cells after siRNA interference. Result: siRNA successfully reduced the exPreliminary study on a novel biomarker of PARP inhibitorspression of PNKP protein in SW480 cells and PNKP inhibitor PP23 effectively inhibited the proliferation of SW480 cells, which both enhanced the sensitivity of SW480 to Olaparib. Conclusion: Decreasing the expression of PNKP protein and blocking the function of PNKP protein both enhance the sensitivity of SW480 cells to Olaparib and it suggests that the sensitivity of SW480 to PARP inhibitors is related to PNKP protein.
李侃、龚笑海、金坚、李喆、朱景宇
药学基础医学分子生物学
分子药理学PARP抑制剂PNKP奥拉帕尼生物标志物
Molecular PharmacologyPARP inhibitorsPNKPOlaparibbiomarker
李侃,龚笑海,金坚,李喆,朱景宇.PARP抑制剂新型生物标志物的初步研究[EB/OL].(2019-05-21)[2025-07-21].http://www.paper.edu.cn/releasepaper/content/201905-213.点此复制
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