Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia.

Oncotarget2024PMID: 38588464

View on PubMed DOI: 10.18632/oncotarget.28579

Plain Language Summary

Researchers tested whether the GHRH antagonist MIA-602 could overcome drug resistance in acute myeloid leukemia (AML) cells that had become resistant to the chemotherapy drug doxorubicin. MIA-602 was equally effective against both normal and drug-resistant versions of three AML cell lines, and it also reduced tumor growth in mice implanted with resistant leukemia cells. This suggests MIA-602 could be valuable for treating AML patients whose cancer has stopped responding to standard chemotherapy.

Abstract

Acute myeloid leukemia (AML) is characterized by the rapid proliferation of mutagenic hematopoietic progenitors in the bone marrow. Conventional therapies include chemotherapy and bone marrow stem cell transplantation; however, they are often associated with poor prognosis. Notably, growth hormone-releasing hormone (GHRH) receptor antagonist MIA-602 has been shown to impede the growth of various human cancer cell lines, including AML. This investigation examined the impact of MIA-602 as monotherapy and in combination with Doxorubicin on three Doxorubicin-resistant AML cell lines, KG-1A, U-937, and K-562. Theresults revealed a significant reduction in cell viability for all treated wild-type cells. Doxorubicin-resistant clones were similarly susceptible to MIA-602 as the wild-type counterpart. Ourexperiment of xenografted nude mice with Doxorubicin-resistant K-562 revealed a reduction in tumor volume with MIA-602 treatment compared to control. Our study demonstrates that these three AML cell lines, and their Doxorubicin-resistant clones, are susceptible to GHRH antagonist MIA-602.

Authors

Gaumond, Simonetta I; Abdin, Rama; Costoya, Joel; Schally, Andrew V; Jimenez, Joaquin J

Keywords

AMLMIA-602growth hormone-releasing hormoneleukemiaresistance