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姜黄素抑制体内皮肤鳞状细胞癌肿瘤生长。

Curcumin inhibits skin squamous cell carcinoma tumor growth in vivo.

机构信息

Department of Otolaryngology–Head & Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.

出版信息

Otolaryngol Head Neck Surg. 2011 Jul;145(1):58-63. doi: 10.1177/0194599811400711.

Abstract

OBJECTIVE

Squamous cell carcinoma (SCCa) has increased from 4% to 10% over 4 decades, stimulating interest in developing novel agents that slow sun-damaged skin progression. This is the first study evaluating the naturally occurring bioactive food compound curcumin on skin cancer xenografts. Low bioavailability of curcumin has slowed its transition to clinical trials. It is hypothesized that curcumin has growth-inhibitory effects through the TOR pathway and chemopreventive potential in skin SCCa where local application could bypass bioavailability problems.

STUDY DESIGN

A randomized experimental animal and laboratory study.

SETTING

Louisiana State University Health Sciences Center, Shreveport, Louisiana.

SUBJECTS AND METHODS

SCID mice were pretreated with 0, 5, or 15 mg of curcumin (n = 8 per group), 3 days prior to injecting 10⁶ SRB12-p9 skin SCCa cells in each flank, and were gavaged daily thereafter. Tumor volumes were measured and tumors were harvested on day 24 when mice were sacrificed. Immunohistochemical analysis of pS6 expression (n = 3 per group) and tumor volumes in the 3 groups were compared using 1-way analysis of variance and pairwise comparisons were determined with the Tukey t test if overall comparisons were significant.

RESULTS

Tumor volume increased 2.3 times faster in control mice compared with the group receiving 15 mg of curcumin (P = .0003). A significant difference in average tumor volumes was seen (P = .0012), especially with treatment of 15 mg of curcumin compared with control P = .0003). Curcumin inhibited S6 phosphorylation (P = .0027), suggest-ing inhibition of the MTOR pathway.

CONCLUSION

Curcumin appears to inhibit skin SCCa growth and blocks tumor progression by inhibiting pS6 even when gavage is used to deliver curcumin, indicating even more significant effects in future experiments with local application.

摘要

目的

鳞状细胞癌(SCCa)在过去 40 年中从 4%增加到 10%,这激发了人们对开发新型药物的兴趣,这些药物可以减缓受阳光损伤皮肤的进展。这是第一项评估天然生物活性食品化合物姜黄素对皮肤癌异种移植物的研究。姜黄素的生物利用度低,阻碍了其向临床试验的转化。研究假设姜黄素通过 TOR 途径具有生长抑制作用,并且在皮肤 SCCa 中具有化学预防潜力,局部应用可以绕过生物利用度问题。

研究设计

一项随机的动物实验和实验室研究。

设置

路易斯安那州立大学健康科学中心,什里夫波特,路易斯安那州。

研究对象和方法

SCID 小鼠在注射 10⁶ SRB12-p9 皮肤 SCCa 细胞到每侧之前,用 0、5 或 15mg 姜黄素预处理(每组 8 只),并在其后每天灌胃。测量肿瘤体积,并在第 24 天处死小鼠时采集肿瘤。对每组 3 只小鼠的 pS6 表达免疫组化分析(n = 3 只/组)和肿瘤体积进行比较,采用单因素方差分析进行比较,如果总比较有意义,则采用 Tukey t 检验进行两两比较。

结果

与接受 15mg 姜黄素的组相比,对照组小鼠的肿瘤体积增长速度快 2.3 倍(P =.0003)。平均肿瘤体积有显著差异(P =.0012),特别是与对照组相比,接受 15mg 姜黄素的组差异显著,P =.0003)。姜黄素抑制 S6 磷酸化(P =.0027),表明 MTOR 途径受到抑制。

结论

即使通过灌胃给予姜黄素,姜黄素似乎也能抑制皮肤 SCCa 的生长,并通过抑制 pS6 阻止肿瘤进展,这表明在未来的局部应用实验中会有更显著的效果。

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