The combination of methionine adenosyltransferase 2A inhibitor and methyltransferase like 3 inhibitor promotes apoptosis of non-small cell lung cancer cells and produces synergistic anti-tumor activity.

Methionine adenosyltransferase 2 A (MAT2A) mediates the synthesis of methyl donor S-Adenosylmethionine (SAM), providing raw materials for methylation reactions in cells. MAT2A inhibitors are currently used for the treatment of tumors with methylthioadenosine phosphorylase (MTAP) deficiency in clinical research. Methyltransferase like 3 (METTL3) catalyzes N6-methyladenosine (mA) modification of mRNA in mammalian cells using SAM as the substrate which has been shown to affect the tumorigenesis of non-small cell lung cancer (NSCLC) from multiple perspectives.

Proteasome inhibitors reduce CD73 expression partly via decreasing p-ERK in NSCLC cells.

Ecto-5'-nucleotidase (CD73), encoded by the NT5E gene, mediates tumor immunosuppression and has been targeted for the development of new anticancer drugs. Proteasome inhibitors impair protein degradation by inhibiting proteasome and have been used in the clinic for cancer therapy. Here we report that proteasome inhibitors reduce the protein and mRNA levels of CD73.