载顺铂靶向纳米微泡对小细胞肺癌增殖抑制作用的实验研究  

Inhibitory effect of targeting nanobubbles with cisplatin loading on small cell lung cancer proliferation

作　　者：王金萍[1] 李荣山[2] 严继萍[1] 肖瑞琳 Wang Jinping;Li Rongshan;Yan Jiping;Xiao Ruilin(Department of Ultrasound,Shanxi Province People′s Hospital,Taiyuan 030012,China;Department of Nephrology,Shanxi Province People′s Hospital,Taiyuan 030012,China;Department of Biochemistry and Molecular Biology,School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西省人民医院超声科,太原030012 [2]山西省人民医院肾内科,太原030012 [3]山西医科大学基础医学院生物化学与分子生物学教研室,太原030001

出　　处：《中华超声影像学杂志》2022年第1期75-81,共7页Chinese Journal of Ultrasonography

基　　金：山西省自然科学基金面上青年项目(201901D211523);山西省教育厅高校科技创新计划(2020L0187);中国超声医师科技新星计划课题(KJXX2021001)。

摘　　要：目的制备载顺铂抗前胃泌素释放肽(ProGRP)单抗靶向纳米微泡,并研究其对小细胞肺癌(SCLC)增殖抑制效果及抗癌的分子机制。方法应用薄膜水化法制备载顺铂抗ProGRP单抗靶向纳米微泡,研究其理化性质;建立10只SCLC裸鼠皮下移植瘤模型,以空白纳米微泡作对照,分析载顺铂靶向纳米微泡的超声分子靶向显影效果;另建24只SCLC荷瘤裸鼠模型,随机分为4组:空白纳米微泡组、顺铂组、载顺铂纳米微泡组、载顺铂靶向纳米微泡组,计算抑瘤率。采用CCK8法检测其对SCLC增殖的影响;运用RT-PCR和Western blotting分析4个处理组SCLC增殖相关基因P53、Rb、c-myc的mRNA和蛋白水平变化。结果成功制备载顺铂抗ProGRP单抗靶向纳米微泡,粒径为(467.3±42.3)nm,结构稳定;载顺铂靶向纳米微泡在SCLC裸鼠移植瘤体内具有良好的超声分子显影效果,可明显抑制SCLC增殖;RT-PCR和Western blotting显示,与对照组相比,载顺铂靶向纳米微泡组的增殖相关基因P53、Rb的mRNA和蛋白水平显著上调,c-myc的mRNA和蛋白水平显著下调(均P<0.05)。结论载顺铂靶向纳米微泡对SCLC具有抑制增殖的作用,可作为一种治疗SCLC的新型潜在靶向药物。Objective To prepare cisplatin-loaded anti-progastrin-releasing peptide(ProGRP)monoclonal antibody targeted nanobubbles,and to explore the proliferation inhibition effect and anti-cancer molecular mechanism of them on small cell lung cancer(SCLC).Methods The cisplatin targeted nanobubbles were prepared by thin film hydrating method,and the physicochemical property were explored.The subcutaneous xenograft tumor models of SCLC in 10 nude mice were established,and the ultrasound molecular targeting development effect of cisplatin targeted nanobubbles was analyzed by using blank nanobubbles as control.Another 24 tumor-bearing nude mouse models were established and randomly divided into four groups:blank nanobubbles group,cisplatin group,cisplatin nanobubbles group,cisplatin targeted nanobubbles group.The tumor inhibition rate was calculated.The effect on SCLC proliferation was detected by CCK8 method.RT-PCR and Western blotting methods were used to detect SCLC proliferation related genes the P53,Rb,c-myc protein and mRNA expression level of change,the molecular regulatory mechanism was analyzed.Results The cisplatin targeted nanobubbles were successfully prepared.The particle size was(467.3±42.3)nm,the structure was stable.The cisplatin targeted nanobubbles had a good effect of ultrasonic molecular development in SCLC xenograft.Compared with the control group,the proliferation of SCLC cells was significantly inhibited by cisplatin targeted nanobubbles.The RT-PCR and Western blotting analysis showed that compared with the control group,the mRNA and protein levels of the proliferation-related gene P53 and Rb in the cisplatin targeted nanovesicles group were significantly up-regulated,and the mRNA and protein levels of c-myc were significantly down-regulated(all P<0.05).Conclusions The cisplatin targeted nanobubbles can inhibit the proliferation of SCLC,and may be used as a new potential targeted drug for the treatment of SCLC.

关 键 词：超声分子显像 顺铂 靶向纳米微泡 小细胞肺癌 增殖 

分 类 号：R734.2[医药卫生—肿瘤]