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Oncol Rep. 2016 Dec;36(6):3363-3370. doi: 10.3892/or.2016.5183. Epub 2016 Oct 19.

Fentanyl induces autophagy via activation of the ROS/MAPK pathway and reduces the sensitivity of cisplatin in lung cancer cells.

Author information

1
Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
2
Department of Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
3
Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Dalian, Liaoning 116011, P.R. China.
4
Department of Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310012, P.R. China.
5
Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.

Abstract

Cancer pain is the most common complication of lung carcinoma. Opioid agonist fentanyl is widely used for relieving pain in cancer patients, and cisplatin (DDP)‑based chemotherapy is commonly used for the treatment of advanced lung cancer; these two drugs are always used together in lung carcinoma patients. However, the mechanisms and related biological pathways by which fentanyl influences cisplatin sensitivity are relatively poorly reported. Here, we found that fentanyl reduces the sensitivity of cisplatin in human lung cancer cells and induces autophagy. Fentanyl induced reactive oxygen species (ROS) generation and JNK activation. N-acetyl‑L‑cysteine is a ROS scavenger and antioxidant, and the inhibition of JNK with SP600125 prevented fentanyl‑induced autophagy. We also found that 3-methyladenine (3-MA; an autophagy inhibitor) increased the sensitivity of DDP and weakened the inhibition of fentanyl. In conclusion, fentanyl reduces the sensitivity of cisplatin in lung cancer cells through the ROS-JNK-autophagy pathway, whereas the autophagy inhibitor 3-MA may weaken this effect.

PMID:
27779694
DOI:
10.3892/or.2016.5183
[Indexed for MEDLINE]

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