NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia

Cell cycle dysregulation and the corresponding metabolic reprogramming play significant roles in tumor development and progression. CDK9, a kinase that regulates gene transcription and cell cycle, also induces oncogene transcription and abnormal cell cycle in AML cells. The function of CDK9 for gene...

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Main Authors: Qing Zhu, Jia Cheng, Yuqing Gao, Zimu Zhang, Jian Pan, Xin Su, Danhong Fei, Linbo Cai, Juanjuan Yu, Yanling Chen, Wanyan Jiao, Di Wu, Xiaolu Li, Peifang Xiao
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Cancer Biology & Therapy
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Online Access:https://www.tandfonline.com/doi/10.1080/15384047.2025.2450859
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author Qing Zhu
Jia Cheng
Yuqing Gao
Zimu Zhang
Jian Pan
Xin Su
Danhong Fei
Linbo Cai
Juanjuan Yu
Yanling Chen
Wanyan Jiao
Di Wu
Xiaolu Li
Peifang Xiao
author_facet Qing Zhu
Jia Cheng
Yuqing Gao
Zimu Zhang
Jian Pan
Xin Su
Danhong Fei
Linbo Cai
Juanjuan Yu
Yanling Chen
Wanyan Jiao
Di Wu
Xiaolu Li
Peifang Xiao
author_sort Qing Zhu
collection DOAJ
description Cell cycle dysregulation and the corresponding metabolic reprogramming play significant roles in tumor development and progression. CDK9, a kinase that regulates gene transcription and cell cycle, also induces oncogene transcription and abnormal cell cycle in AML cells. The function of CDK9 for gene regulation in AML cells requires further exploration. In this study, we knocked down the CDK9 to investigate its effects on the growth and survival of AML cells. Through RNA-seq analysis, we identified that in U937 cells CDK9 regulates numerous genes involved in proliferation and apoptosis, including mTOR, SREBF1, and Bcl-2. Furthermore, our results demonstrated that both CDK9 and FASN are crucial for the proliferation and survival of Kasumi-1 and U937 cells. Mechanistically, MCL1, c-Myc, and Akt/mTOR/SREBF1 may be critical factors and pathways in the combined therapy of NVP-2 and Orlistat. In summary, our study revealed that CDK9 and FASN are vital for maintaining AML cell survival and proliferation. Treatment with NVP-2 and Orlistat may be a promising clinical candidate for patients with AML.
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institution Kabale University
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publishDate 2025-12-01
publisher Taylor & Francis Group
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spelling doaj-art-8f96f96f8b0c47f7b3c82a6960054a732025-01-13T04:09:53ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762025-12-0126110.1080/15384047.2025.2450859NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemiaQing Zhu0Jia Cheng1Yuqing Gao2Zimu Zhang3Jian Pan4Xin Su5Danhong Fei6Linbo Cai7Juanjuan Yu8Yanling Chen9Wanyan Jiao10Di Wu11Xiaolu Li12Peifang Xiao13Children’s Hospital of Soochow University, Suzhou, ChinaChildren’s Hospital of Soochow University, Suzhou, ChinaInstitute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, ChinaInstitute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, ChinaInstitute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Hematology, Children’s Hospital of Soochow University, Suzhou, ChinaChildren’s Hospital of Soochow University, Suzhou, ChinaChildren’s Hospital of Soochow University, Suzhou, ChinaChildren’s Hospital of Soochow University, Suzhou, ChinaChildren’s Hospital of Soochow University, Suzhou, ChinaChildren’s Hospital of Soochow University, Suzhou, ChinaInstitute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, ChinaInstitute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Hematology, Children’s Hospital of Soochow University, Suzhou, ChinaCell cycle dysregulation and the corresponding metabolic reprogramming play significant roles in tumor development and progression. CDK9, a kinase that regulates gene transcription and cell cycle, also induces oncogene transcription and abnormal cell cycle in AML cells. The function of CDK9 for gene regulation in AML cells requires further exploration. In this study, we knocked down the CDK9 to investigate its effects on the growth and survival of AML cells. Through RNA-seq analysis, we identified that in U937 cells CDK9 regulates numerous genes involved in proliferation and apoptosis, including mTOR, SREBF1, and Bcl-2. Furthermore, our results demonstrated that both CDK9 and FASN are crucial for the proliferation and survival of Kasumi-1 and U937 cells. Mechanistically, MCL1, c-Myc, and Akt/mTOR/SREBF1 may be critical factors and pathways in the combined therapy of NVP-2 and Orlistat. In summary, our study revealed that CDK9 and FASN are vital for maintaining AML cell survival and proliferation. Treatment with NVP-2 and Orlistat may be a promising clinical candidate for patients with AML.https://www.tandfonline.com/doi/10.1080/15384047.2025.2450859Acute myeloid leukemiaapoptosisCDK9cell proliferationc-MycFASN
spellingShingle Qing Zhu
Jia Cheng
Yuqing Gao
Zimu Zhang
Jian Pan
Xin Su
Danhong Fei
Linbo Cai
Juanjuan Yu
Yanling Chen
Wanyan Jiao
Di Wu
Xiaolu Li
Peifang Xiao
NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia
Cancer Biology & Therapy
Acute myeloid leukemia
apoptosis
CDK9
cell proliferation
c-Myc
FASN
title NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia
title_full NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia
title_fullStr NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia
title_full_unstemmed NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia
title_short NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia
title_sort nvp 2 in combination with orlistat represents a promising therapeutic strategy for acute myeloid leukemia
topic Acute myeloid leukemia
apoptosis
CDK9
cell proliferation
c-Myc
FASN
url https://www.tandfonline.com/doi/10.1080/15384047.2025.2450859
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