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

Abstract

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.

Keywords:

• Lactate dehydrogenase A inhibitor
• gemcitabine
• carboplatin
• malignant mesothelioma

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was funded by the National Science Center of Poland (2018/31/B/NZ7/02909) and by a young investigator grant from the Purine and Pyrimidine Society.