Pan Yunbao, Liu Dong, Wei Yongchang, Su Dan, Lu Chenyang, Hu Yanchao, Zhou Fuling
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityWuhan, China.
Department of Clinical Pharmacy, Baoji Central HospitalBaoji, China.
Front Pharmacol. 2017 Jun 12;8:359. doi: 10.3389/fphar.2017.00359. eCollection 2017.
Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.
急性髓系白血病(AML)是一种在大多数成年人中常见的急性白血病;其患病率随年龄增长而增加。由于治疗耐药性,AML的总体生存率非常低。壬二酸(AZA)无毒、无致畸性且无致突变性,其对各种肿瘤细胞的抗肿瘤作用已得到充分证实;然而,其在AML细胞中的治疗效果在很大程度上尚不清楚。在本研究中,结果表明AZA以剂量依赖性方式显著抑制AML细胞的活力并诱导其凋亡。此外,AZA抑制磷酸化Akt、Jab1和Trx的表达,并且用Jab1 siRNA处理可增强这种抑制作用。此外,AZA使AML细胞对阿糖胞苷化疗敏感。通过在裸鼠肿瘤模型中皮下接种AML细胞来检测AZA对肿瘤生长的抑制作用。这些发现表明AZA作为抗肿瘤活性的有效成分是有用的。