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

κ阿片受体激动剂对非小细胞肺癌(NSCLC)细胞生长的影响

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作者:N Kuzumaki, A Suzuki, M Narita, T Hosoya, A Nagasawa, S Imai, K Yamamizu, H Morita, H Nagase, Y Okada, H J Okano, J K Yamashita, H Okano, T Suzuki, M Narita

Background

It is becoming increasingly recognised that opioids are responsible for tumour growth. However, the effects of opioids on tumour growth have been controversial.

Conclusion

The present results showed that stimulation of KOR reduces the growth of gefitinib-resistant NSCLC cells through the activation of GSK3β.

Methods

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.

Results

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).

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