Combined Treatment with Evogliptin and Temozolomide Alters miRNA Expression but Shows Limited Additive Effect on Glioma

TL;DR

Combining evogliptin and temozolomide slightly reduces glioma cell viability and changes miRNA levels, but the combined effect is not strongly additive.

Contribution

The study reveals miRNA expression changes from evogliptin and temozolomide combination therapy in glioma models.

Findings

Combination therapy reduced cell viability more than single-agent treatments in glioma cell lines.

miRNAs like miR-4440 and miR-6780b-5p were upregulated following treatment with evogliptin or the combination.

Evogliptin alone did not improve survival in the mouse xenograft model.

Abstract

Dipeptidyl-peptidase IV (DPP4) inhibitors have shown potential anti-tumor properties. This study investigates the therapeutic potential of evogliptin, a DPP4 inhibitor, both as a single agent and in combination with temozolomide (TMZ), in glioma models. In vitro studies were performed using U87 and U373 glioma cell lines exposed to different concentrations of TMZ (250, 500 μM) and evogliptin (250, 500 ng/mL), either alone or together, for 24, 48, and 72 h. Cell viability was determined with the MTT assay. In vivo effectiveness was tested in a xenograft mouse model treated with intraperitoneal injections of evogliptin (60 mg/k g/day), TMZ (15 mg/kg/day), or their combination over 3 weeks. The combination of TMZ and evogliptin markedly reduced cell viability compared to single-agent treatments. DPP4 mRNA levels decreased more substantially with combination therapy. miRNA expression profiling with Affymetrix arrays indicated that certain miRNAs, such as miR-4440 and miR-6780b-5p, were upregulated after treatment with evogliptin or the combination regimen, whereas others were downregulated. These miRNAs could play a role in limiting glioma growth through DPP4 regulation. In the animal model, evogliptin alone did not provide a survival advantage. Analysis of TCGA data showed that glioma patients with decreased DPP4 expression had improved survival rates. The co-administration of evogliptin and temozolomide resulted in distinct miRNA profile changes. Nevertheless, both in vitro and in vivo, the added cytotoxicity from the combination was minimal.

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