Synergistic Effects of PI3K and c-Myc Co-targeting in Acute Leukemia: Shedding New Light on Resistance to Selective PI3K-δ Inhibitor CAL-101

被引：12
|
作者：
Riyahi, Niknam [1 ]
Safaroghli-Azar, Ava [1 ]
Sheikh-Zeineddini, Negar [1 ]
Sayyadi, Mohamad [1 ]
Bashash, Davood [2 ]
机构：
[1] Shahid Beheshti Univ Med Sci, Dept Hematol & Blood Banking, Sch Allied Med Sci, Student Res Comm, Tehran, Iran
[2] Shahid Beheshti Univ Med Sci, Dept Hematol & Blood Banking, Sch Allied Med Sci, Tehran, Iran
来源：
CANCER INVESTIGATION | 2019年 / 37卷 / 07期
关键词：
Acute leukemia; c-Myc; PI3K pathway; CAL-101; 10058-F4; CELLS; APOPTOSIS; 10058-F4; PROLIFERATION; PROGRESSION; TELOMERASE; TRANSITION; MECHANISM; AUTOPHAGY; PATHWAYS;
D O I：
10.1080/07357907.2019.1651328
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Enthusiasms into the application of PI3K-delta inhibitor CAL-101 has been muted due to the over-activation of compensatory molecules. Our results delineated that c-Myc suppression using 10058-F4 enhanced CAL-101 cytotoxicity in less sensitive cells through different mechanisms based on p53 status; while CAL-101-plus-10058-F4 induced G1 arrest in wild-type p53-expressing leukemic cells, no conspicuous increase in G1 was noted in U937 cells harboring mutant p53. Conclusively, this study shed lights on the role of c-Myc oncoprotein in acute leukemia cells sensitivity to PI3K inhibitor and outlined that the combination of c-Myc inhibitor and CAL-101 may be a promising therapeutic approach in leukemia.
引用
收藏
页码：311 / 324
页数：14
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