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Morphine Suppresses Lung Cancer Cell Proliferation Through the Interaction with Opioid Growth Factor Receptor: An In
Ji Yeon Kim1, Hyun Joo Ahn, Jin Kyoung Kim
1From the *Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; and †Department of Thoracic and Cardiovascular surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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.
Insights
Morphine may suppress lung cancer growth by binding to the opioid growth factor receptor (OGFR). This receptor, a negative regulator of cell proliferation, is expressed in lung cancer tissues and cell lines.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Inconsistent reports exist regarding opioid effects on lung cancer growth.
- The opioid growth factor receptor (OGFR) is identified as a negative regulator of cell proliferation.
Purpose of the Study:
- To investigate the role of OGFR in morphine-induced lung cancer growth suppression.
- To determine if OGFR is a binding site for morphine.
Main Methods:
- Assessed OGFR expression in human lung cancer tissues and cell lines via immunohistochemistry and RT-PCR.
- Utilized the H1975 lung cancer cell line (adenocarcinoma) for interaction and growth studies.
- Verified morphine-OGFR binding and morphine's impact on cancer cell proliferation.
Main Results:
- OGFR is expressed in lung cancer tissues and cell lines, with higher expression in adenocarcinoma.
- OGFR expression inversely correlated with cell proliferation.
- Morphine treatment reduced H1975 cell number by ~23% and suppressed growth in the S phase.
- Morphine-OGFR binding was confirmed, and growth suppression was attenuated upon OGFR knockdown.
Conclusions:
- Lung cancer tissues and cell lines express OGFR.
- Morphine interacts with OGFR, suggesting a mechanism for suppressing lung cancer progression.
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