探讨 GHRH 拮抗剂 MIA-602 在克服急性髓系白血病多柔比星耐药中的作用。
Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia.
机构信息
Dr. Philip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA.
出版信息
Oncotarget. 2024 Apr 8;15:248-254. doi: 10.18632/oncotarget.28579.
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. The results 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. Our experiment 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.
急性髓细胞白血病（AML）的特征是骨髓中突变的造血祖细胞快速增殖。常规疗法包括化疗和骨髓干细胞移植，但它们通常与预后不良相关。值得注意的是，生长激素释放激素（GHRH）受体拮抗剂 MIA-602 已被证明可阻碍包括 AML 在内的多种人类癌细胞系的生长。本研究考察了 MIA-602 单药治疗和联合多柔比星对三种多柔比星耐药 AML 细胞系 KG-1A、U-937 和 K-562 的影响。结果表明，所有经处理的野生型细胞的细胞活力均显著降低。多柔比星耐药克隆与野生型细胞一样容易受到 MIA-602 的影响。我们用多柔比星耐药 K-562 进行的异种移植裸鼠实验表明，与对照组相比，MIA-602 治疗可减少肿瘤体积。我们的研究表明，这三种 AML 细胞系及其多柔比星耐药克隆对 GHRH 拮抗剂 MIA-602 敏感。
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