Morphine Suppresses Lung Cancer Cell Proliferation Through the Interaction with Opioid Growth Factor Receptor: An In Vitro and Human Lung Tissue Study.

BACKGROUND

There have been inconsistent reports on whether opioids promote or inhibit lung cancer growth. In this study, we suggest that opioid growth factor receptor (OGFR), a negative regulator of cell proliferation, is a binding site of morphine and is involved in subsequent morphine-induced lung cancer growth suppression.

METHODS

The expression and distribution of OGFR in human lung cancer tissues and cell lines were assessed with immunohistochemistry and real-time reverse transcription polymerase chain reaction. The human lung cancer cell line, H1975 (adenocarcinoma), which overexpressed OGFR but not μ-opioid receptors, was selected for further analysis to verify the interaction between morphine and OGFR and the impact of morphine on cancer cell growth.

RESULTS

OGFR was expressed in lung cancer tissues and all cancer cell lines tested. Adenocarcinoma showed a higher OGFR expression than squamous cell carcinoma (reverse transcription polymerase chain reaction relative quantitation value: median [interquartile range], 13.1 [9.3-20.0] vs 4.3 [2.2-6.6]; P = 0.003). OGFR expression showed an inverse correlation with cell proliferation (r = -0.92, P = 0.0001). Morphine treatment reduced the median H1975 cell number by approximately 23% (P = 0.03). Growth suppression by morphine was attenuated when OGFR was knocked down. A confocal experiment demonstrated binding of morphine to OGFR. Growth suppression by morphine occurred in the S phase of the cell cycle.

CONCLUSIONS

Lung cancer tissues and cell lines express OGFR. Morphine interacts with OGFR and may suppress lung cancer progression.