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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,P<0.05。与DDP组对比,p53mRNA在NDP组均降低,P<0.05;p53蛋白表达在NDP低剂量组和NDP中剂量组中均降低(P<0.05),而在NDP高剂量组中表达差异无统计学意义,P>0.05。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。
Objective Nedaplatin (NDP) is the second generation of platinum compounds. Its anti-tumor mechanism is the same as that of Cisplatin (DDP). Adverse reactions such as renal and gastrointestinal tract are less than DDP and do not require hydration. Convenience. This study was to investigate the inhibitory effect of NDP on the nude mice MGC-803 gastric cancer xenografts and its effect on p53 gene expression. Methods MGC-803 gastric cancer tumor-bearing nude mice model was established. MGC-803 human gastric cancer cell line was inoculated nude mice for about 1 week. When the tumor grew to a diameter of 5 ~ 9mm, it was randomly divided into blank control group, DDP group and NDP low And high dose group, 8 rats in each group. The rats were injected intraperitoneally with normal saline, cisplatin and different doses of nedaplatin (1.0, 2.0 and 3.0 mg / kg) respectively. The expression of p53 gene in the tumor was detected by Western blotting and RT-PCR. Results The expression of p53 mRNA in the blank control group, DDP group and NDP low, medium and high dose groups were 0.297 ± 0.024,0.892 ± 0.098,0.444 ± 0.016,0.561 ± 0.034 and 0.585 ± 0.021, respectively. The expression of p53 protein in the blank control group, DDP group and NDP low, medium and high dose groups were 0.295 ± 0.027, 0.541 ± 0.032, 0.316 ± 0.034, 0.408 ± 0.028 and 0.525 ± 0.041, respectively. The relative expression of p53 mRNA and protein in DDP group and NDP group was higher than that in control group (P <0.05). Compared with DDP group, the expression of p53 mRNA in NDP group was significantly lower than that in NDP group (P <0.05). The expression of p53 protein in NDP group and NDP group was lower than that in DDP group (P <0.05), but not in NDP group Significance, P> 0.05. Compared with different concentration of NDP chemotherapy group, p53 mRNA and protein expression level showed a dose-response relationship, that is, as the dose of the drug increased, its expression increased. Conclusion NDP can increase the expression of p53 mRNA and protein in MGC-803 gastric cancer bearing tumor, but no obvious advantage compared with DDP.