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Peroxisome proliferator-activated receptor γ improves pemetrexed therapeutic efficacy in non-squamous non-small cell lung cancer.

Year: 2021
Type: article
Abstract: OBJECTIVE: The folic acid analog pemetrexed (PMX) is recommended for the first-line chemotherapy for advanced non-squamous non-small cell lung cancer (NSCLC). However, the mechanisms underlying PMX cytotoxicity in NSCLC remain to be fully explored. METHODS: PMX effect was evaluated in a urethane-induced lung adenocarcinoma mouse model. The interaction between PMX and intracellular proteins, particularly peroxisome proliferator-activated receptor γ (PPARγ), was investigated. The role of PPARγ in mediating pemetrexed cytotoxicity was investigated using NSCLC cell lines, mouse models and clinical specimens. RESULTS: . PMX inhibited tumor growth by activating PPARγ in a urethane-induced lung cancer model characterized by elevated NF-κB activity. CONCLUSION: PPARγ improves pemetrexed therapeutic efficacy in non-squamous NSCLC. The cytotoxicity effect of PMX can be synergized by activating PPARγ and thereby inhibiting NF-κB pathway.
Authors: Tianxing Hang, Li Yang, Xiujuan Zhang, Jing Li, Feng Long, Ning Zhu, Ying Li, Jingwen Xia, Youzhi Zhang, Peng Zhang, Yuanyuan Zhang, Xiaomin Wei, Shengqing Li
Institutions: Nanjing University of Chinese Medicine, Fudan University, Nanjing Second Hospital, Huashan Hospital, Second Military Medical University, Shanghai Changzheng Hospital, Second Peoples Hospital of Shaanxi Province
Language: English
Open Access status: green
OpenAlex ID: W3160963076
FWCI: 0.358
Cites: 31
Cited by: 6
Related to: 10