Effect of κ-opioid receptor agonist on the growth of non-small cell lung cancer (NSCLC) cells.

Effect of κ-opioid receptor agonist on the growth of non-small cell lung cancer (NSCLC) cells.
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κ阿片受体激动剂对非小细胞肺癌(NSCLC)细胞生长的影响。

DOI:
10.1038/bjc.2011.574
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发表时间:
2012-03-13
影响因子:
8.8
通讯作者:
Narita, M.
Narita, M.
中科院分区:
医学1区
文献类型:
--
作者:
Kuzumaki, N.;Suzuki, A.;Narita, M.;Hosoya, T.;Nagasawa, A.;Imai, S.;Yamamizu, K.;Morita, H.;Nagase, H.;Okada, Y.;Okano, H. J.;Yamashita, J. K.;Okano, H.;Suzuki, T.;Narita, M.

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人们越来越认识到阿片类药物是肿瘤生长的原因。然而,阿片类药物对肿瘤生长的影响一直存在争议。采用细胞增殖实验观察κ-阿片受体(KOR)激动剂对非小细胞肺癌(NSCLC)细胞生长的影响。进行蛋白质印迹以确定用KOR激动剂治疗抑制肿瘤生长的机制。将选择性KOR激动剂U 50,488 H加入吉非替尼敏感(HCC 827)和吉非替尼耐药(H1975)NSCLC细胞中,使其生长呈浓度依赖性下降。这些影响被取消的共同治疗与选择性KOR拮抗剂nor-BNI。此外,吉非替尼在HCC 827细胞中的生长抑制作用通过与U 50,488 H共处理而进一步增强。在抑制肿瘤生长方面,向H1975细胞中添加U 50,488 H导致磷酸化糖原合成酶激酶3β(p-GSK 3 β)浓度依赖性降低。目前的结果表明,KOR的刺激通过激活GSK 3 β降低吉非替尼耐药NSCLC细胞的生长。
It is becoming increasingly recognised that opioids are responsible for tumour growth. However, the effects of opioids on tumour growth have been controversial. The effects of κ-opioid receptor (KOR) agonist on the growth of non-small cell lung cancer (NSCLC) cells were assessed by a cell proliferation assay. Western blotting was performed to ascertain the mechanism by which treatment with KOR agonist suppresses tumour growth. Addition of the selective KOR agonist U50,488H to gefitinib-sensitive (HCC827) and gefitinib-resistant (H1975) NSCLC cells produced a concentration-dependent decrease in their growth. These effects were abolished by co-treatment with the selective KOR antagonist nor-BNI. Furthermore, the growth-inhibitory effect of gefitinib in HCC827 cells was further enhanced by co-treatment with U50,488H. With regard to the inhibition of tumour growth, the addition of U50, 488H to H1975 cells produced a concentration-dependent decrease in phosphorylated-glycogen synthase kinase 3β (p-GSK3β). The present results showed that stimulation of KOR reduces the growth of gefitinib-resistant NSCLC cells through the activation of GSK3β.
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