奈达铂对裸鼠MGC-803胃癌移植瘤抑制作用及对p53基因表达影响
本文选题:奈达铂 + 顺铂 ; 参考:《中华肿瘤防治杂志》2016年19期
【摘要】:目的奈达铂(Nedaplatin,NDP)是第2代铂类化合物,抗肿瘤的机制与顺铂(Cisplatin,DDP)相同,其肾脏和胃肠道等不良反应均小于DDP,且无需水化,使用方便。本研究探讨NDP对裸鼠MGC-803胃癌移植瘤的抑制作用及对p53基因表达的影响。方法制备MGC-803胃癌荷瘤裸鼠模型,MGC-803人胃癌细胞株接种裸鼠约1周时间,待肿瘤生长至直径约5~9mm随机分为空白对照组、DDP组和NDP低、中和高剂量组,每组8只。分别予以腹腔注射生理盐水、顺铂、不同剂量奈达铂(1.0、2.0和3.0 mg/kg),采用蛋白质印迹法及RT-PCR法检测瘤体中p53基因的表达。结果空白对照组、DDP组和NDP低、中和高剂量组p53mRNA表达量分别为0.297±0.024、0.892±0.098、0.444±0.016、0.561±0.034和0.585±0.021。空白对照组、DDP组和NDP低、中和高剂量组p53蛋白表达量分别为0.295±0.027、0.541±0.032、0.316±0.034、0.408±0.028和0.525±0.041。p53mRNA及蛋白在DDP组和NDP组相对表达量均高于空白对照组,P0.05。与DDP组对比,p53mRNA在NDP组均降低,P0.05;p53蛋白表达在NDP低剂量组和NDP中剂量组中均降低(P0.05),而在NDP高剂量组中表达差异无统计学意义,P0.05。NDP不同浓度化疗组间比较,p53mRNA及蛋白表达水平呈量效关系,即随着药物剂量增大,其表达量增高。结论NDP能增加MGC-803胃癌荷瘤裸鼠肿瘤组织p53mRNA及蛋白表达水平,但与DDP相比未见明显优势。
[Abstract]:Objective Nedaplatin (NDP) is the second generation platinum compound with the same antitumor mechanism as cisplatin Cisplatin (DDP). The adverse reactions in kidney and gastrointestinal tract of Nedaplatin NDP are less than those of DDP, and they need no hydration and are easy to use. The aim of this study was to investigate the inhibitory effect of NDP on xenografts of MGC-803 gastric carcinoma in nude mice and its effect on p53 gene expression. Methods Human gastric cancer cell line MGC-803 was inoculated into nude mice for about 1 week. When the tumor grew to a diameter of about 5~9mm, it was randomly divided into two groups: control group (n = 8) and control group (n = 8) with low, medium and high doses of NDP. Intraperitoneal injection of normal saline, cisplatin, and different doses of nidaplatin 1.0 mg / kg and 3.0 mg / kg 路kg ~ (-1) respectively. The expression of p53 gene was detected by Western blotting and RT-PCR assay. Results the expression of p53mRNA in the control group was lower than that in the control group. The expression of p53mRNA in the middle and high dose groups was 0.297 卤0.024 卤0.098 卤0.444 卤0.016, 0.561 卤0.034 and 0.585 卤0.021, respectively. The relative expression of p53 protein in DDP group and NDP group was significantly higher than that in DDP group and NDP group. The expression levels of p53 protein in the control group were 0.295 卤0.027, 0.541 卤0.032, 0.316 卤0.034, 0.408 卤0.028 and 0.525 卤0.041.p53mRNA, respectively. The relative expression levels of p53 protein in the DDP group and the NDP group were higher than those in the control group. Compared with DDP group, the expression of p53 protein in NDP group was significantly lower than that in NDP group. The expression of p53 protein in NDP low dose group and NDP medium dose group was decreased, but there was no significant difference in NDP high dose group. There was a dose-effect relationship between different concentrations of P0.05.NDP chemotherapy group and the expression level of p53mRNA and protein. That is, with the increase of drug dose, its expression increased. Conclusion NDP can increase the expression of p53mRNA and protein in tumor tissues of nude mice bearing MGC-803 gastric cancer, but there is no obvious advantage compared with DDP.
【作者单位】: 莱芜市人民医院肿瘤科;莱芜市人民医院普外科;莱芜市妇幼保健院;
【分类号】:R735.2
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