The Therapeutic Effect of a Novel GAPDH Inhibitor in Mouse Model of Breast Cancer and Efficacy Monitoring by Molecular Imaging

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2024 May 29

PMID 38811918

Authors

Yun-Qi Zhang

Wei Zhang

Xiang-Tai Kong

Wang-Xi Hai

Rui Guo

Min Zhang

Su-Lin Zhang

Biao Li

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer is a serious threat to women's health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells.

Methods: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model.

Results: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor F-FDG and F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group.

Conclusions: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. F-FDG and F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163.

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