白细胞介素-1受体拮抗剂可抑制体内皮下B16黑色素瘤的生长。

Interleukin-1 receptor antagonist inhibits subcutaneous B16 melanoma growth in vivo.

作者信息

McKenzie R C, Oran A, Dinarello C A, Sauder D N

机构信息

Department of Dermatology, University of Edinburgh, Scotland, UK.

出版信息

Anticancer Res. 1996 Jan-Feb;16(1):437-41.

PMID:8615650

Abstract

BACKGROUND

Previously we demonstrated that injection of Interleukin-alpha (IL-1) stimulated B16 melanoma tumour growth in vivo, associated with increased intercellular adhesion molecule-1 (ICAM-1) expression on the tumour cells (Photodermatol Photoimmunol Photomed 1994; 10: 74-79, ).

METHODS

In the present study, we examined the effect of blocking IL-1 receptors - by addition of recombinant Interleukin-1 receptor antagonist (IL-1RA) - on melanoma tumour growth in vivo and in vitro.

RESULTS

Subcutaneous co-injection of IL-1RA with B16 tumour cells into C57BL/6 mice, followed by injection of IL-1RA every second day reduced tumour growth significantly from day 18 to day 33 post-injection. Treatment with IL-1RA appeared to have a bi-phasic effect, low doses being more effective than dosed > 1 microgram/mouse. After 33 days, mice treated with 1.0 or 0.1 micrograms/2nd day had significantly smaller tumours than controls (p < 0.05), however, mice treated with 10 micrograms had tumours no different in size from those of untreated controls. However, survival of IL-RA-treated mice was not significantly different between treatment groups. Addition of IL-1RA to B16 cultures in vitro caused a small dose-dependent decrease in cell growth. Maximum inhibition (64% of control numbers) was observed after 48h in media containing > or = 10 ng/ml Il-1RA (p < 0.05). Using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), we examined the expression of ICAM-1 message in B16 cells treated in culture with 10 ng/ml IL-1RA or 10 ng/ml IL-1 alpha for 6h or 24h. In IL-1-treated cultures ICAM-1 mRNA expression was increased to 161% of control levels. After 24h, ICAM-1 message was 198% control levels (p = 0.0008). Treatment with IL-1RA reduced the constitutive ICAM-1 expression to 75% of basal after 6h and to 68% of basal after 24h 9 (p = 0.011).

CONCLUSION

Abrogation of IL-1 activity, in combination with other systemic therapies may prove useful in the treatment of melanoma.

摘要

背景

此前我们证明，注射白细胞介素-α（IL-1）可刺激B16黑色素瘤在体内生长，这与肿瘤细胞上细胞间黏附分子-1（ICAM-1）表达增加有关（《光皮肤病学、光免疫学与光医学》，1994年；10：74 - 79）。

方法

在本研究中，我们通过添加重组白细胞介素-1受体拮抗剂（IL-1RA）来阻断IL-1受体，研究其对黑色素瘤在体内和体外生长的影响。

结果

将IL-1RA与B16肿瘤细胞皮下共同注射到C57BL/6小鼠体内，随后每隔一天注射IL-1RA，从注射后第18天到第33天，肿瘤生长显著减缓。IL-1RA治疗似乎具有双相效应，低剂量比大于1微克/小鼠的剂量更有效。33天后，每隔一天接受1.0或0.1微克治疗的小鼠肿瘤明显小于对照组（p < 0.05），然而，接受10微克治疗的小鼠肿瘤大小与未治疗的对照组无差异。但是，各治疗组中接受IL-RA治疗的小鼠存活率无显著差异。在体外向B16培养物中添加IL-1RA导致细胞生长出现小剂量依赖性下降。在含有≥1０纳克/毫升IL-1RA的培养基中培养48小时后观察到最大抑制（为对照数量的64%）（p < 0.05）。使用半定量逆转录-聚合酶链反应（RT-PCR），我们检测了在培养物中用10纳克/毫升IL-1RA或10纳克/毫升IL-1α处理6小时或24小时的B16细胞中ICAM-1信息的表达。在IL-1处理的培养物中，ICAM-1 mRNA表达增加至对照水平的161%。24小时后，ICAM-1信息为对照水平的198%（p = 0.0008）。用IL-1RA处理6小时后，组成型ICAM-1表达降至基础水平的75%，24小时后降至基础水平的68%（p = 0.011）。