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. The in vitro 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 in vivo 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.
摘要:
急性髓性白血病(AML)的特征是骨髓中诱变造血祖细胞的快速增殖。常规疗法包括化疗和骨髓干细胞移植;然而,它们通常与不良预后相关。值得注意的是,生长激素释放激素(GHRH)受体拮抗剂MIA-602已被证明可以阻止各种人类癌细胞系的生长,包括AML。这项研究检查了MIA-602作为单一疗法并与多柔比星联合对三种多柔比星抗性AML细胞系的影响,KG-1A,U-937和K-562.体外结果显示所有处理的野生型细胞的细胞活力显著降低。多柔比星抗性克隆与野生型对应物一样对MIA-602敏感。我们对多柔比星抗性K-562的异种移植裸鼠的体内实验显示,与对照组相比,MIA-602治疗的肿瘤体积减少。我们的研究表明,这三种AML细胞系,和他们的多柔比星抗性克隆,对GHRH拮抗剂MIA-602敏感。