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The Application of GHRH Antagonist as a Treatment for Resistant APL.

Ravinder S ChaleStephanie M AlmeidaMario RodriguezIvan JozicSimonetta I GaumondAndrew V SchallyJoaquin J Jimenez
Published in: Cancers (2023)
GHRH is a hypothalamic peptide shown to stimulate the proliferation of malignant cells in humans. We have previously shown that the use of GHRH antagonist MIA-602 successfully suppressed the growth of many human cancer cell lines, spanning more than 20 types of cancers. In this study, we demonstrate the presence of GHRH-R in the NB4, NB4-RAA, and K-562 model cell lines. Furthermore, we demonstrate the inhibited proliferation of all three cell lines in vitro after incubation with MIA-602. The treatment of xenografts of human APL cell lines with MIA-602 led to a significant reduction in tumor growth. Additionally, combination therapy with both doxorubicin (DOX) and MIA-602 showed a marked synergistic effect in reducing the proliferation of the K-562 AML cell line. These findings suggest that MIA-602 could be utilized to address resistance to all- trans retinoic acid (ATRA) and arsenic trioxide (ATO) therapies, as well as in augmenting anthracycline-based regimens.
Keyphrases
  • combination therapy
  • endothelial cells
  • signaling pathway
  • induced apoptosis
  • induced pluripotent stem cells
  • squamous cell carcinoma
  • acute myeloid leukemia
  • cell cycle arrest
  • heavy metals
  • smoking cessation