Therapeutic targeting of PFKFB3 and PFKFB4 in multiple myeloma cells under hypoxic conditions.

ABSTRACT: The treatment of multiple myeloma (MM) patients has been dramatically changed by the introduction of new agents; however, many patients relapse. Hypoxia is a critical component of the bone-marrow microenvironment. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) is responsible for maintaining cellular levels of fructose-2,6-bisphosphate, which regulates glycolysis. We found that the gene expressions of PFKFB3 and PFKFB4 were elevated under hypoxic conditions. Treatments with the PFKFB3 inhibitor, PFK158, and PFKFB4 inhibitor, 5MPN, were found to inhibit the growth of myeloma cells. The combined treatment of myeloma cells with carfilzomib and PFK158 or 5MPN was more cytotoxic than either drug alone. Caspase 3/7 activity and cellular cytotoxicity were also increased. In addition,

SUBMITTER: Okabe S 

PROVIDER: S-EPMC9109357 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature