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肌醇六磷酸(IP6)抑制黑色素瘤细胞的增殖。

Inositol hexaphosphate (IP6) inhibits cellular proliferation in melanoma.

作者信息

Rizvi Irfan, Riggs Dale R, Jackson Barbara J, Ng Alex, Cunningham Cynthia, McFadden David W

机构信息

Department of Surgery, Robert C. Byrd Health Science Center, West Virginia University, Morgantown, West Virginia 26506, USA.

出版信息

J Surg Res. 2006 Jun 1;133(1):3-6. doi: 10.1016/j.jss.2006.02.023. Epub 2006 Mar 23.

Abstract

BACKGROUND

Inositol Hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate found in food sources high in fiber content. We have previously reported IP6 to have significant inhibitory effects against pancreatic cancer in vitro. We hypothesized that the IP6 would significantly inhibit cell growth of cutaneous melanoma in vitro.

MATERIALS AND METHODS

The melanoma line HTB68 was cultured using standard techniques and treated with IP6 at doses ranging from 0.2 to 1.0 mM/well. Cell viability was measured by MTT at 72 h. VEGF production was measured in the cell supernatants by ELISA. Apoptosis was evaluated by Annexin V-FITC and results calculated using FACS analysis. Statistical analysis was performed by ANOVA.

RESULTS

Significant reductions (P < 0.001) in cellular proliferation were observed with IP6. Overall, IP6 exhibited a mean inhibition of cell growth of 52.1 +/- 11.5% (range, 1.6-83.0%) at 72 h of incubation. VEGF production was significantly reduced (P < 0.001) by the addition of IP6 (7.5 pg/ml) compared to control (40.9 pg/ml). IP6 significantly increased (P = 0.029) late apoptosis from 5.3 to 7.0% gated events. No changes in necrosis or early apoptosis were observed.

CONCLUSIONS

Adjuvant treatment of melanoma continues to challenge clinicians and patients. Our findings that IP6 significantly decreased cellular growth, VEGF production and increased late apoptosis in melanoma suggest its potential therapeutic value. Further in vivo studies are planned to evaluate safety and clinical utility of this agent.

摘要

背景

肌醇六磷酸(IP6)是一种天然存在的多磷酸化碳水化合物,存在于高纤维含量的食物来源中。我们之前报道过IP6在体外对胰腺癌具有显著的抑制作用。我们假设IP6在体外会显著抑制皮肤黑色素瘤的细胞生长。

材料与方法

采用标准技术培养黑色素瘤细胞系HTB68,并用浓度范围为0.2至1.0 mM/孔的IP6进行处理。72小时时通过MTT法测定细胞活力。通过ELISA法测定细胞上清液中的VEGF产生量。通过膜联蛋白V-FITC评估细胞凋亡,并使用流式细胞术分析计算结果。采用方差分析进行统计分析。

结果

观察到IP6使细胞增殖显著降低(P < 0.001)。总体而言,在孵育72小时时,IP6对细胞生长的平均抑制率为52.1 +/- 11.5%(范围为1.6-83.0%)。与对照组(40.9 pg/ml)相比,添加IP6(7.5 pg/ml)后VEGF产生量显著降低(P < 0.001)。IP6使晚期凋亡从5.3%显著增加至7.0%(门控事件)(P = 0.029)。未观察到坏死或早期凋亡的变化。

结论

黑色素瘤的辅助治疗仍然是临床医生和患者面临的挑战。我们的研究结果表明,IP6可显著降低黑色素瘤细胞的生长、VEGF产生量并增加晚期凋亡,提示其潜在的治疗价值。计划进一步开展体内研究以评估该药物的安全性和临床实用性。

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