上海交通大学学报（医学版）

›› 2011, Vol. 31 ›› Issue (5): 588-.doi: 10.3969/j.issn.1674-8115.2011.05.014

• 论著（基础研究） • 上一篇    下一篇

米托蒽醌对大鼠胃癌基因PCNA、Caspase-3和p53基因表达的影响

杨宏梅, 邢 影, 郑美珍   

  1. 辽宁省肿瘤医院内科, 沈阳 110042
  • 出版日期:2011-05-28 发布日期:2011-05-27
  • 作者简介:杨宏梅（1971—）, 女, 副主任医师, 博士；电子信箱: ZJO5314784@163.com。

Effects of Mitoxantrone on expression of PCNA, Caspase-3 and p53 genes in rats with gastric cancer

YANG Hong-mei, XING Ying, ZHENG Mei-zhen   

  1. Department of Internal Medicine, Liaoning Cancer Hospital &|Institute, Shenyang 110042, China
  • Online:2011-05-28 Published:2011-05-27

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摘要：

目的 研究米托蒽醌对胃癌大鼠病变胃黏膜增殖细胞核抗原（PCNA）、Caspase-3和p53基因表达的影响。方法 制作N-甲基-N′-硝基-N-亚硝基胍（MNNG）诱发的大鼠胃癌模型，实验分为空白对照组（N组）、模型对照组（M组）、小剂量米托蒽醌干预组（ML组）及大剂量米托蒽醌干预组（MH组），每组25只动物。免疫组织化学S-P法检测胃癌组织中PCNA的表达，分光光度计法检测Caspase-3活性，Real-Time PCR和Western blotting检测p53基因和蛋白的表达情况。结果 N组PCNA表达阴性，ML组和MH组的PCNA阳性率显著低于M组（P<0.01，P<0.05）。M组和MH组的Caspase-3活性均显著低于N组（P<0.01，P<0.05）；但ML组和MH组的Caspase-3活性又显著高于M组（P<0.01，P<0.05）。M组的p53基因表达明显高于N组（P<0.01）；ML组和MH组的p53基因表达逐渐降低（P<0.01，P<0.05），但仍高于N组。p53蛋白的表达量在M组、ML组和MH组中依次下降。结论 米托蒽醌可能通过改变基因的表达达到治疗胃癌的效果，对抑制或逆转癌症的发展具有一定的作用。

关键词: 米托蒽醌, 增殖细胞核抗原, Caspase-3, p53, 胃癌

Abstract:

Objective To investigate the effects of Mitoxantrone on the expression of proliferating cell nuclear antigen (PCNA), Caspase-3 and p53 genes in gastric mucosa of rats with gastric cancer. Methods Rat models of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer were established, and blank control group (group N), model control group (group M), small dose Mitoxantrone group (group ML) and mega dose Mitoxantrone group (group MH) were divided, with 25 rats in each group. The expression of PCNA in tissues of gastric cancer was detected by immunohistochemical S-P method, the activity of Caspase-3 was determined by spectrophotometry, and the expression of p53 gene and protein was detected by Real-Time PCR and Western blotting, respectively. Results There was no expression of PCNA in group N, and the expression of PCNA in group ML and group MH was significantly lower than that in group M (P<0.01, P<0.05). The activity of Caspase-3 in group M and group MH was significantly lower than that in group N (P<0.01, P<0.05), while the expression of Caspase-3 in group ML and group MH was significantly higher than that in group M (P<0.01, P<0.05). The expression of p53 gene in group M was significantly higher than that in group N (P<0.01). The expression of p53 gene in group ML and group MH gradually decreased （P<0.01, P<0.05）,while was still higher than that in group N. The expression of p53 protein in group M was higher than that in group ML, and the expression of p53 protein in group MH was lower than that in group ML. Conclusion Mitoxantrone is effective in the treatment of rats with gastric cancer by changing the expression of genes, which may inhibit or reverse the development of cancer.

Key words: Mitoxantrone, proliferating cell nuclear antigen, Caspase-3, p53, gastric cancer