OPIOID AND NICOTINE RECEPTORS AFFECT GROWTH-REGULATION OF HUMAN LUNG-CANCER CELL-LINES
OPIOID AND NICOTINE RECEPTORS AFFECT GROWTH-REGULATION OF HUMAN LUNG-CANCER CELL-LINES
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DOI：
10.1073/pnas.87.9.3294
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发表时间：
1990-05-01
影响因子：
11.1
通讯作者：
MINNA, JD
中科院分区：
文献类型：
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作者：
MANECKJEE, R;MINNA, JD
利用特异性配体，我们发现不同组织学类型的肺癌细胞系表达多个高亲和力（Kd = 10-9-10-10 M）的膜受体。德尔塔和卡帕。阿片类激动剂以及尼古丁和-班加罗毒素。这些受体具有生物活性，因为在阿片类药物和尼古丁应用后，肺癌细胞中的cAMP水平降低。尼古丁浓度（.apprxeq.）100 nM)对体外肺癌细胞生长无明显影响，而100 μ m。德尔塔和卡帕。低浓度阿片类激动剂（1 ~ 100 nM）体外抑制肺癌生长。我们还发现肺癌细胞表达免疫反应性阿片肽(. β。-内啡肽，脑啡肽或肌啡肽)，表明阿片类药物参与负自分泌循环或肿瘤抑制系统。由于肺癌患者几乎普遍暴露于尼古丁，我们测试了尼古丁是否影响肺癌细胞对阿片类药物生长的反应，发现100-200 nM浓度的尼古丁部分或完全逆转了9/14种肺癌细胞系阿片类药物诱导的生长抑制。这些对肺癌细胞的体外实验结果表明，阿片类药物可能是“肿瘤抑制”系统的一部分，而尼古丁可以在肺癌的发病机制中规避这一系统。
Using specific ligands, we find that lung cancer cell lines of diverse histologic types express multiple, high-affinity (Kd = 10-9-10-10 M) membrane receptors for .mu., .delta., and .kappa. opioid agonists and for nicotine and .alpha.-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations (.apprxeq. 100 nM) found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas .mu., .delta., and .kappa. opioid agonists at low concentrations (1-100 nM) inhibited lung cancer growth in vitro. We also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides (.beta.-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, we tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a "tumor suppressor" system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.