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肌肽在 NIH3T3-HER2/neu 小鼠模型体内延缓肿瘤生长。

Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model.

机构信息

Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig und Medizinische Fakultät der Universität Leipzig, Leipzig, Germany.

出版信息

Mol Cancer. 2010 Jan 6;9:2. doi: 10.1186/1476-4598-9-2.

DOI:10.1186/1476-4598-9-2
PMID:20053283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2818694/
Abstract

BACKGROUND

It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy.

RESULTS

A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 microl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects proliferation in vivo.

CONCLUSION

As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.

摘要

背景

先前的研究表明二肽肌肽能够抑制从恶性神经胶质瘤患者分离出的培养细胞的生长。在本研究中,我们研究了肌肽是否也会影响体内肿瘤的生长,从而可以考虑将其用于人类癌症治疗。

结果

我们使用小鼠模型来研究肌肽是否可以抑制体内肿瘤的生长。因此,将条件性表达人表皮生长因子受体 2(HER2/neu)的 NIH3T3 成纤维细胞植入裸鼠背部皮肤,比较治疗动物和对照动物的肿瘤生长情况。在两个独立的实验中,接受肿瘤细胞的裸鼠每天接受 500 微升 1 M 肌肽溶液的腹腔内注射。注射后 12 天可检测到可测量的肿瘤。接受 NaCl 溶液腹腔内注射的对照动物的侵袭性肿瘤生长在第 16 天开始,而接受肌肽治疗的小鼠的侵袭性生长则延迟,从第 19 天开始。直至第 24 天,肌肽对肿瘤生长的显著作用。虽然肌肽不能完全阻止肿瘤生长,但对肿瘤的显微镜检查显示,肌肽治疗动物的肿瘤有丝分裂数明显减少(p < 0.0003),证实肌肽会影响体内的增殖。

结论

作为一种天然存在的物质,具有很强的抑制体内恶性细胞生长的潜力,肌肽应被视为一种潜在的抗癌药物。为了进一步了解肌肽在分子水平上的作用,还需要进行更多的实验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383e/2818694/35fe4153a640/1476-4598-9-2-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383e/2818694/2b2d5afcddef/1476-4598-9-2-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383e/2818694/9b9e528243f7/1476-4598-9-2-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383e/2818694/35fe4153a640/1476-4598-9-2-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383e/2818694/2b2d5afcddef/1476-4598-9-2-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383e/2818694/9b9e528243f7/1476-4598-9-2-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383e/2818694/35fe4153a640/1476-4598-9-2-3.jpg

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Low HER2-expressing glioblastomas are more often secondary to anaplastic transformation of low-grade glioma.
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