Propofol regulates METTL3-mediated PARP-1 m6A modification to promote Parthanatos to improve NSCLC chemotherapy resistance
Year: 2026
Type: article
Abstract: This study aimed to investigate the molecular mechanism by which propofol enhances chemosensitivity in non-small cell lung cancer (NSCLC). In vitro experiments were performed to evaluate the effects of propofol on NSCLC cell lines and to elucidate the underlying molecular mechanisms. In vivo, A549/DDP cells were subcutaneously injected into nude mice, followed by cisplatin (DDP) treatment, and tumor tissues were subsequently analyzed by hematoxylin–eosin staining and immunohistochemistry. Our results demonstrated that propofol significantly enhanced the sensitivity of A549/DDP cells to cisplatin by promoting Parthanatos. This process was characterized by increased apoptosis-inducing factor (AIF) and macrophage migration inhibitory factor (MIF) binding and nuclear translocation, loss of mitochondrial membrane potential, nicotinamide adenine dinucleotide (NAD + ) depletion, accumulation of poly(ADP-ribose) (PAR), and increased expression of the DNA damage marker phosphorylated histone H2AX (γH2AX). Moreover, propofol treatment was associated with elevated interleukin-6 (IL-6) levels. Mechanistically, overexpression of methyltransferase-like 3 (METTL3) enhanced PARP-1 m 6 A modification and Parthanatos activation, whereas METTL3 knockdown exerted the opposite effects. Furthermore, propofol enhanced cisplatin sensitivity by regulating METTL3-mediated m 6 A modification of PARP-1 in vitro, which was further confirmed in vivo. In conclusion, propofol enhances cisplatin chemosensitivity in NSCLC by activating Parthanatos through modulation of METTL3-mediated PARP-1 m 6 A modification. These findings provide mechanistic insight into propofol-mediated reversal of chemoresistance and identify the METTL3–PARP-1–Parthanatos axis as a potential therapeutic target in NSCLC.
Source: Scientific Reports
Authors: Quan Ling, Kepeng Liu, Junlin Wen, Jin Liu, Yong Chen
Institution: Zhongshan People's Hospital
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7133768971