Lung but not brain cancer cell malignancy inhibited by commonly used anesthetic propofol during surgery: Implication of reducing cancer recurrence risk

Abstract

Introduction: Intravenous anesthesia with propofol was reported to improve cancer surgical outcomes when compared with inhalational anesthesia. However, the underlying molecular mechanisms largely remain unknown.

Objectives: The anti-tumor effects of propofol and the possible underlying mechanism including altered metabolic and signaling pathways were studied in the current study.

Methods: The cell viability, proliferation, migration, and invasion of cancer cells were analyzed with CCK-8, Ki-67 staining, wound healing, and Transwell assay, respectively. The protein changes were analyzed with Western blot and immunofluorescent staining. The metabolomics alteration was studied with ¹H-NMR spectroscopy. The gene expression regulations were analyzed with PCR gene array and qRT-PCR experiments.

Results: In this study, we found that propofol reduced cell viability and inhibited cell proliferation, migration and invasion of lung cancer cells, but not neuroglioma cells. In lung cancer cells, propofol downregulated glucose transporter 1 (GLUT1), mitochondrial pyruvate carrier 1 (MPC1), p-Akt, p-Erk1/2, and hypoxia- inducible factor 1 alpha (HIF-1 α ) expressions and upregulated pigment epithelium-derived factor (PEDF) expression. Propofol increased intracellular glutamate and glycine but decreased acetate and formate whilst increased glucose, lactate, glutamine, succinate, pyruvate, arginine, valine, isoleucine, and leucine and glycerol, and decreased acetate, ethanol, isopropanol in the culture media of lung cancer cells. Furthermore, VEGFA, CTBP1, CST7, CTSK, CXCL12, and CXCR4 gene expressions were downregulated, while NR4A3, RB1, NME1, MTSS1, NME4, SYK, APC, and FAT1 were upregulated following the propofol treatment. Consistent with the phenotypical changes, these molecular and metabolic changes were not found in the neuroglioma cells.

Conclusion: Our findings indicated anti-tumor effects of propofol on the lung cancer but not brain cancer, through the regulation of tumor metastasis-related genes, multi-cellular signaling and cellular metabolism.

Keywords: Brain cancer; HIF-1α; Intravenous anesthetic; Lung cancer; PEDF.