一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> ACS Biomaterials Science & Engineering >>article
ACS Biomaterials Science & Engineering

ACS Biomaterials Science & Engineering

IF: 5.4
Download PDF

GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia

Published:3 March 2021 DOI: 10.1038/s41419-021-03504-2 PMID: 33658491
Cheng Zhou,?Juan Du,?Liang Zhao,?Wei Liu,?Tianming Zhao,?Hui Liang,?Peng Fang,?Kaixuan Zhang,?Hui Zeng

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy with high incidence and recurrence rates. Gene expression profiling has revealed that transcriptional overexpression of glioma-associated oncogene 1 (GLI1), a vital gene in the Hedgehog (Hh) signaling pathway, occurs in poor-prognosis AML, and high levels of phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) and AKT3 predict shorter overall survival in AML patients. In this study, we discovered that GLI1 overexpression promotes cell proliferation and reduces chemotherapy sensitivity in AML cells while knocking down GLI1 has the opposite effect. Moreover, GLI1 promoted cell cycle progression and led to elevated protein levels of cyclins and cyclin-dependent kinases (CDKs) in AML cells. By luciferase assays and co-immunoprecipitation, we demonstrated that the PI3K/AKT pathway is directly activated by GLI1. GLI1 overexpression significantly accelerates tumor growth and upregulated p-AKT, CDK4, and cyclinD3 in vivo. Notably, the GLI1 inhibitor GANT61 and the CDK4/6 inhibitor PD 0332991 had synergistic effects in promoting Ara-c sensitivity in AML cell lines and patient samples. Collectively, our data demonstrate that GLI1 reduces drug sensitivity by regulating cell cycle through the PI3K/AKT/GSK3/CDK pathway, providing a new perspective for involving GLI1 and CDK4/6 inhibitors in relapsed/refractory (RR) patient treatment.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
MK-2206 2HCl 1032350-13-2 C25H22ClN5O 265 suppliers $10.00-$5132.00
MK-2206 2HCl 1032350-13-2 C25H22ClN5O 265 suppliers $10.00-$5132.00
MK-2206 2HCl 1032350-13-2 C25H22ClN5O 265 suppliers $10.00-$5132.00
MK-2206 2HCl 1032350-13-2 C25H22ClN5O 265 suppliers $10.00-$5132.00

Similar articles

IF:3.2

PKN2 Promotes Peripheral Nerve Repair by Regulating Autophagy via Activation of the AKT‐mTOR Pathway: An In Vitro Study

Journal of Biochemical and Molecular Toxicology Lin Wang, Yuan‐sheng Huang,etc Published: 22 November 2024
IF:5.7

The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironment.

Frontiers in Immunology Lanyang Gao, Lei Zhu,etc Published: 1 January 2023
IF:5.4

Protective effects and mechanism of puerarin targeting PI3K/Akt signal pathway on neurological diseases.

ACS Applied Energy Materials Qian Wang, Zi-Nuo Shen,etc Published: 24 October 2022
古丈县| 苗栗县| 育儿| 南城县| 东乌珠穆沁旗| 通许县| 龙岩市| 谢通门县| 阳谷县| 台东县| 奉化市| 泸州市| 石景山区| 双鸭山市| 临颍县| 什邡市| 获嘉县| 蕉岭县| 漳州市| 临清市| 陈巴尔虎旗| 龙游县| 上栗县| 托克托县| 大丰市| 油尖旺区| 石屏县| 阳信县| 柞水县| 平原县| 建昌县| 九寨沟县| 金门县| 古丈县| 西贡区| 抚顺县| 平塘县| 浮山县| 成武县| 黄平县| 紫阳县|