δ 阿片受体激动剂对 HCT-8/E11 结肠癌细胞侵袭相关活性的直接影响。
Direct effects of delta opioid receptor agonists on invasion-associated activities of HCT-8/E11 colon cancer cells.
机构信息
Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University, De Pintelaan 185, 9000 Gent, Belgium.
出版信息
Anticancer Res. 2010 Jan;30(1):9-17.
BACKGROUND
Opioids and opioid receptors are an integral part of the tumour microenvironment and hence may influence tumour progression. Studies on direct effects of opioids on invasion-associated cellular activities are equivocal. We wanted to clarify these differences.
MATERIALS AND METHODS
The direct effects of the delta opioid receptor (DOR) agonists [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE), leu-enkephalin and [D-Ala(2), D-Leu(5)]-enkephalin (DADLE) on invasion-associated activities of HCT-8 myc-DOR and HCT-8 FLAG-DOR colon cancer cells stably overexpressing DOR were studied.
RESULTS
The opioids showed a trend to stimulate invasion of single cells in collagen in one clone, while they did not influence invasion of the other clone. In other invasion assays, no effects were observed. They did not affect cell growth and homotypical cell-cell adhesion. DPDPE at 0.1 muM inhibited directional migration; the other opioids and concentrations tested were inefficient.
CONCLUSION
Opioids differently influence invasion-associated cellular activities, depending on the expression level of DOR, experimental set-up, type and concentration of opioid.
背景
阿片类药物和阿片受体是肿瘤微环境的一个组成部分，因此可能影响肿瘤的进展。关于阿片类药物对侵袭相关细胞活性的直接影响的研究结果存在争议。我们想要澄清这些差异。
材料和方法
研究了 δ 型阿片受体（DOR）激动剂[D-Pen(2), D-Pen(5)]-脑啡肽（DPDPE）、亮啡肽和[D-Ala(2), D-Leu(5)]-脑啡肽（DADLE）对稳定过表达 DOR 的 HCT-8 myc-DOR 和 HCT-8 FLAG-DOR 结肠癌细胞侵袭相关活性的直接影响。
结果
阿片类药物在一个克隆中显示出刺激胶原中单细胞侵袭的趋势，而在另一个克隆中则没有影响。在其他侵袭实验中，没有观察到影响。它们不影响细胞生长和同质细胞-细胞黏附。0.1 μM 的 DPDPE 抑制定向迁移；而其他测试的阿片类药物和浓度则无效。
结论
阿片类药物根据 DOR 的表达水平、实验设置、阿片类药物的类型和浓度，不同程度地影响侵袭相关的细胞活性。
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