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黄花棘豆生物碱对H22肝癌荷瘤小鼠生长抑制及PCNA和p53表达的影响

The effect of alkaloid from Oxytropis ochrocephala on growth inhibition and expression of PCNA and p53 in mice bearing H22 Hepatocellular Carcinoma.

作者信息

Long Ling, Li Qingwang

机构信息

College of Animal Science, Northwest Agriculture and Forestry University, Shannxi Province, People's Republic of China.

出版信息

Yakugaku Zasshi. 2005 Aug;125(8):665-70. doi: 10.1248/yakushi.125.665.

DOI:10.1248/yakushi.125.665
PMID:16079618
Abstract

To study the antitumor activity of alkaloid extracted from Oxytropis ochrocephala and its possible mechanism, we observed the effect of alkaloid on tumor weight and expression of PCNA and p53 in mice bearing H(22) hepatocellular carcinoma by means of immunohistochemistry SP method. After treatment with alkaloid from Oxytropis ochrocephala, the results showed that alkaloid administration (25 and 50 mg/kg body weight, p.o.) could inhibit H(22) hepatocellular carcinoma growth to various extent, and the rates of inhibition were 48.5% and 57.7% respectively (p<0.01). The antitumor activity of the alkaloid is in a dose dependent manner, with no signs of toxicity to weight, kidney and liver. The sections of tumor showed the number of tumor cell decreased and nucleus appeared putrescence such as nucleus atrophy, disintegrating and dissolving. Meanwhile, the expression of PCNA and mutant p53 protein positive cell numbers in mice bearing H(22) hepatocellular carcinoma also suppressed by alkaloid (p<0.05). It suggested that Alkaloid from Oxytropis ochrocephala showed antitumor effect and its possible mechanism might be associated with the expression inhibition of PCNA and mutant p53 protein. Further studies are needed to explore the antitumor activity of the other compounds of Oxytropis ochrocephala and to specify their possible mechanism of action.

摘要

为研究黄花棘豆生物碱的抗肿瘤活性及其可能机制,采用免疫组织化学SP法观察该生物碱对H(22)肝癌荷瘤小鼠肿瘤重量及PCNA和p53表达的影响。黄花棘豆生物碱处理后,结果显示,生物碱给药(25和50mg/kg体重,口服)能不同程度抑制H(22)肝癌生长,抑制率分别为48.5%和57.7%(p<0.01)。生物碱的抗肿瘤活性呈剂量依赖性,对体重、肾脏和肝脏无毒性迹象。肿瘤切片显示肿瘤细胞数量减少,细胞核出现坏死,如核萎缩、解体和溶解。同时,黄花棘豆生物碱也抑制了H(22)肝癌荷瘤小鼠中PCNA和突变型p53蛋白阳性细胞数的表达(p<0.05)。提示黄花棘豆生物碱具有抗肿瘤作用,其可能机制可能与抑制PCNA和突变型p53蛋白的表达有关。需要进一步研究以探索黄花棘豆其他化合物的抗肿瘤活性并明确其可能的作用机制。

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