Propofol Triggers Cell Death in Lung Cancer Cells by Increasing PANX1 Expression, Activating the Mitochondrial Cell Death Pathway, and Enhancing ROS Levels.

Abstract

Background: Lung cancer treatment remains a global challenge due to tumor cell resistance. Propofol, traditionally used as an anesthetic, has demonstrated potential anti-tumor properties. This study seeks to elucidate how propofol induces cell death in lung cancer cells by upregulating Pannexin 1 (PANX1) expression, activating the mitochondrial cell death pathway, and augmenting reactive oxygen species (ROS) production.

Methods: In this study, the A549 lung cancer cell line was employed as the experimental model. Cells underwent exposure to varying propofol concentrations and were pre-treated with H₂O₂ and N-acetylcysteine (NAC) to simulate oxidative stress and antioxidant conditions. Various techniques, including 5-Ethynyl-2'-deoxyuridine (EdU), colony formation, Transwell, 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA), Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL), and JC-1 (5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide) probes, were employed to evaluate propofol's effects on lung cancer cell viability, growth, invasion, ROS levels, apoptosis, and mitochondrial membrane potential. Western blot analysis was used to measure PANX1, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, and Cytochrome C (Cyt C) protein levels. Additionally, PANX1's influence on propofol-induced apoptosis was investigated through siRNA interference.

Results: The experiment unveiled propofol's dose-dependent inhibition of A549 lung cancer cell growth, coupled with decreased cell proliferation and invasion attributable to heightened ROS production. Notably, propofol treatment significantly elevated mitochondrial membrane potential, signifying activation of the mitochondrial cell death pathway (p < 0.01). Furthermore, propofol upregulated PANX1 expression (p < 0.01), thereby intensifying apoptosis signaling, whereas PANX1 inhibition ameliorated propofol-induced apoptosis (p < 0.01). These findings underscore the pivotal role of PANX1 upregulation and ROS augmentation in propofol-induced apoptosis in lung cancer cells.

Conclusion: This study provides evidence that propofol induces cell death in lung cancer cells by upregulating PANX1, activating the mitochondrial apoptosis pathway, and increasing ROS production. These findings suggest that targeting PANX1 and ROS could enhance the anti-cancer efficacy of propofol in lung cancer.