Self-synthesized second mitochondria-derived activator of caspase(SMAC)mimetic TP-WY-1345 enhances the radiosensitivity of NSCLC cells H1299 by targeting anti-apoptotic protein cIAP1
Self-synthesized second mitochondria-derived activator of caspase (SMAC) mimetic TP-WY-1345 enhances the radiosensitivity of NSCLC cells H1299 by targeting anti-apoptotic protein cIAP1作者机构：Institute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China School of Precision Instruments and OPTO-Electronics EngineeringTianjin UniversityTianjin 300072China Key Laboratory for Tibet Plateau Phytochemistry of Qinghai ProvinceCollege of PharmacyQinghai Nationalities UniversityXining 810007China Shanxi Bethune HospitalShanxi Academy of Medical SciencesTaiyuan 030032China Department of Medical UltrasoundThe First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalShandong Medicine and Health Key Laboratory of Abdominal Medical ImagingJinan 250014China
出 版 物：《Radiation Medicine and Protection》 (放射医学与防护（英文）)
年 卷 期：2023年第4卷第1期
页 面：26-32页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：This study was supported by the National Natural Science Foundation of China(31971168 32171239)
主 题：TP-WY-1345 Radiosensitizing SMAC mimetic IAP Non-small cell lung cancer
摘 要：Objective:To explore the toxicity and cellular uptake of the self-synthesized second mitochondria-derived activator of caspase(SMAC)mimetic TP-WY-1345 polypeptide and its radiosensitizing effect on non-small cell lung cancer(NSCLC).Methods:A fluorescence microscope was used to observe the uptake efficiency of TP-WY-1345 by human NSCLC cells *** of the TP-WY-1345 peptide in normal cells was examined in human embryonic lung fibroblasts ***-8 and clone formation experiments were performed to detect the radiosensitizing effect of TP-WY-1345 in the H1299 *** AutoDock Vina simulation software was employed to predict the binding efficiency of TP-WY-1345 to the inhibitor of apoptosis proteins(IAPs).Moreover,Western blot and qPCR experiments were carried out to determine the protein and gene expressions,and the flow cytometry(FCM)technique was used to detect the apoptosis level under different ***:TP-WY-1345 can be self-synthesized,and significant green fluorescence was observed in H12992 h and 6 h after incubation with *** cell counting and CCK-8 results showed that 10μmol/L and 20μmol/L TP-WY-1345 did not produce a significant toxic effect on the MRC5 cells(P0.05).Compared with the single ionizing radiation group,the cell viability and clone formation of H1299 cells were significantly inhibited after treatment with TP-WY-1345 at a concentration of 50μmol/L(P0.05).The sensitivity enhancement ratio(SER)was calculated to be ***,the binding efficiency of TP-WY-1345 to cIAP1 protein was predicted to be7.3,and this strong binding force was demonstrated by Western ***-WY-1345 inhibited the protein and mRNA expressions of cIAP1 and further increased the apoptosis level of the H1299 cells at 24 h(P0.01)and 48 h after radiation(P0.05).Conclusion:SMAC mimetic TP-WY-1345 can enter the H1299 cells and produce a radiosensitizing effect by increasing the level of radiation-induced apoptosis of the ***,TP-WY-1345 i
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