Evaluation of the combination of gemcitabine, carboplatin, and lactate dehydrogenase A inhibitor on malignant mesothelioma

Nucleosides, Nucleotides, & Nucleic Acids 2024 June 20 [Link]

Marika A Frańczak, Federica Borea, Ryszard T Smoleński, Carlotta Granchi, Filippo Minutolo, Elisa Giovannetti, Godefridus J Peters


Objectives: Lactate dehydrogenase A (LDH-A) catalyzes the last step of glycolysis: supplying cells rapidly but inefficiently with ATP. Many tumors, including malignant mesothelioma (MM), have a high expression of LDH-A, which is associated with cancer aggressiveness. We aimed to determine whether the efficacy of the gemcitabine/carboplatin (Gem + Carbo) combination, widely used to treat this disease, could be increased by inhibition of LDH-A (by NHI-2). To this aim, we analyzed the growth inhibition of pleural and peritoneal MM by multiple combinations.

Methods: The 72 h sulforhodamine B assay (SRB) was used to test the cytotoxicity of the combination of gemcitabine (in the range 0.1 – 400 nM) and carboplatin (0.01 – 40 µM) with a fixed concentration of NHI-2 (at IC25). We used pleural (H2452) and primary peritoneal (STO, MESO-II) MM cell lines, cultured at normoxic conditions.

Results: NHI-2 did not increase the cytotoxicity of the combination of 100 nM gemcitabine and 10 µM carboplatin in peritoneal MM cell lines. The cell growth inhibition was 10% smaller after the triple combination than the Gem + Carbo treatment.

Conclusions: Inhibition of LDH-A did not increase the efficacy of gemcitabine and carboplatin in MM under normoxic conditions.