辛伐他汀可抑制鼠黑色素瘤生长。

Simvastatin impairs murine melanoma growth.

机构信息

State University of Ponta Grossa, Biological and Health Science Multidisciplinary Laboratory, Ponta Grossa, Brazil.

出版信息

Lipids Health Dis. 2010 Dec 16;9:142. doi: 10.1186/1476-511X-9-142.

BACKGROUND

Statins induces cell cycle arrest, apoptosis, reduction of angiogenic factors, inhibition of the endothelial growth factor, impairing tissue adhesion and attenuation of the resistance mechanisms. The aim of this study was evaluate the anti-tumoral activity of simvastatin in a B16F10 melanoma-mouse model.

METHODS

Melanoma cells were treated with different concentrations of simvastatin and assessed by viability methods. Melanoma cells (5 × 10(4)) were implanted in two month old C57Bl6/J mice. Around 7 days after cells injection, the oral treatments were started with simvastatin (5 mg/kg/day, p.o.). Tumor size, hematological and biochemical analyses were evaluated.

RESULTS

Simvastatin at a concentration of 0.8 μM, 1.2 μM and 1.6 μM had toxic effect. Concentration of 1.6 μM induced a massive death in the first 24 h of incubation. Simvastatin at 0.8 μM induces early cell cycle arrest in G0/G1, followed by increase of hypodiploidy. Tumor size were evaluated and the difference of treated group and control, after ten days, demonstrates that simvastatin inhibited the tumor expansion in 68%.

CONCLUSION

Simvastatin at 1.6 μM, presented cytototoxicity after 72 h of treatment, with an intense death. In vivo, simvastatin being potentially useful as an antiproliferative drug, with an impairment of growth after ten days.

背景

他汀类药物可诱导细胞周期停滞、凋亡、减少血管生成因子、抑制内皮生长因子、损害组织黏附并减弱耐药机制。本研究旨在评估辛伐他汀在 B16F10 黑色素瘤-小鼠模型中的抗肿瘤活性。

方法

用不同浓度的辛伐他汀处理黑色素瘤细胞，并通过活力测定法进行评估。将黑色素瘤细胞（5×10(4)）注入两个月大的 C57Bl6/J 小鼠。细胞注射后约 7 天，开始用辛伐他汀（5mg/kg/天，口服）进行口服治疗。评估肿瘤大小、血液学和生化分析。

结果

辛伐他汀在 0.8 μM、1.2 μM 和 1.6 μM 的浓度下具有毒性作用。浓度为 1.6 μM 在孵育的前 24 小时内引起大量细胞死亡。辛伐他汀在 0.8 μM 诱导早期细胞周期停滞在 G0/G1 期，随后出现亚二倍体增加。评估肿瘤大小，经过十天后，治疗组与对照组之间的差异表明辛伐他汀抑制了肿瘤的扩张，抑制率为 68%。