Thioridazine Induces Increase in Expression of the Pyruvate Transporter MPC1 Associated with Immune Infiltration in Malignant Tumors.

Abstract

The MPC1 gene is involved in the transport of pyruvate into mitochondria, playing an important role in metabolic processes. Recently, it has been reported that higher MPC1 expression correlates with an increased number of immune cells in human cervical and lung cancers, indicating an enhanced antitumor immune response. Reduced MPC1 levels in gastric tumors are associated with a more severe disease course. Correlational analysis of the MPC1 gene in human lung, hippocampus and frontal cortex tissue samples based on data from the GTEx database revealed associations of this gene with schizophrenia, non-small cell lung cancer, and immune diseases. Our experiments showed that the mRNA level of the MPC1 gene in the non-small cell lung cancer cell line A549 increases 5-fold under the influence of the schizophrenia neuroleptic thioridazine. The observed elevation of MPC1 level may cause tumor infiltration by immune cells, complementing the previously reported data indicating the ability of thioridazine to slow cell growth, induce apoptosis and reduce the ability of cells to migrate.