当前位置: X-MOL 学术Hum. Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
INNO-406 inhibits the growth of chronic myeloid leukemia and promotes its apoptosis via targeting PTEN.
Human Cell ( IF 3.4 ) Pub Date : 2020-08-29 , DOI: 10.1007/s13577-020-00413-y
Jiandong Sun 1 , Yilin Wang 1 , Lirong Sun 1
Affiliation  

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. INNO-406 is a novel tyrosine kinase inhibitor (TKI) that possess specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. The present study aimed to confirm the anti-tumor effect of INNO-406 on CML cells, and elucidate the underlying molecular mechanism. CML cells were treated by INNO-406 at the concentration of 5, 25, 50, 100 μM at the indicated time. Cell proliferation was measured by MTT. Cell apoptosis were detected by Western blot and flow cytometry, respectively. As suggested by the findings, INNO-406 significantly inhibited the proliferation and induced apoptosis of CML cells. In addition, INNO-406 promoted the expression level of PTEN. Rescue experiment revealed that PTEN knockdown reversed the effect of INNO-406 which indicated the correlation between INNO-406 and PTEN. Further study determined that PTEN inhibited the phosphorylation of AKT and 4EBP1 and subsequently altered the expression of apoptotic proteins including bax, cytoplasmic cytochrome c (cyto-c), cleaved caspase3 and bcl-2. In vivo study further confirmed that INNO-406 inhibited the growth of CML cells by targeting PTEN. Based on the above findings, this work extended our understanding of INNO-406 in the therapy of CML and its molecular mechanism.



中文翻译:

INNO-406通过靶向PTEN抑制慢性粒细胞白血病的生长并促进其凋亡。

慢性粒细胞白血病(CML)是一种骨髓增生性肿瘤。INNO-406是一种新型的酪氨酸激酶抑制剂(TKI),具有特定的Lyn激酶抑制活性,对其他肉瘤(Src)家族成员激酶没有或仅有有限的活性。本研究旨在确认INNO-406对CML细胞的抗肿瘤作用,并阐明其潜在的分子机制。在指定的时间用5、25、50、100μM的浓度用INNO-406处理CML细胞。通过MTT测量细胞增殖。通过Western印迹和流式细胞术分别检测细胞凋亡。如发现所提示,INNO-406显着抑制CML细胞的增殖并诱导其凋亡。另外,INNO-406促进了PTEN的表达水平。救援实验表明,PTEN敲低逆转了INNO-406的作用,表明INNO-406与PTEN之间存在相关性。进一步的研究确定PTEN抑制AKT和4EBP1的磷酸化,并随后改变凋亡蛋白的表达,包括bax,胞质细胞色素c(cyto-c),裂解的caspase3和bcl-2。体内研究进一步证实,INNO-406通过靶向PTEN抑制CML细胞的生长。基于上述发现,这项工作扩展了我们对INNO-406在CML治疗及其分子机制中的理解。切割了胱天蛋白酶3和bcl-2。体内研究进一步证实,INNO-406通过靶向PTEN抑制CML细胞的生长。基于以上发现,这项工作扩展了我们对INNO-406在CML治疗及其分子机制中的理解。切割了胱天蛋白酶3和bcl-2。体内研究进一步证实,INNO-406通过靶向PTEN抑制CML细胞的生长。基于上述发现,这项工作扩展了我们对INNO-406在CML治疗及其分子机制中的理解。

更新日期:2020-08-30
down
wechat
bug