title: Fentanyl induces autophagy via activation of the ROS/MAPK pathway and reduces the sensitivity of cisplatin in lung cancer cells.
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.
authors: Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Jiaqi
authors: J
authors: Yao
authors: Department of Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Chi
authors: C
authors: Ma
authors: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Dalian, Liaoning 116011, P.R. China.
authors: Wei
authors: W
authors: Gao
authors: Department of Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310012, P.R. China.
authors: Jinxiao
authors: J
authors: Liang
authors: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Chang
authors: C
authors: Liu
authors: Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Hongfang
authors: H
authors: Yang
authors: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Dalian, Liaoning 116011, P.R. China.
authors: Qiu
authors: Q
authors: Yan
authors: Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Qingping
authors: Q
authors: Wen
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005283:Fentanyl / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D002945:Cisplatin; D005283:Fentanyl