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Title: Application of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy
Authors: Sakamoto, Tetsunori
Ajiro, Masahiko
Watanabe, Akira
Matsushima, Shingo
Ueda, Keiji
Hagiwara, Masatoshi  kyouindb  KAKEN_id
Author's alias: 阪本, 哲紀
網代, 将彦
渡辺, 亮
松島, 慎吾
萩原, 正敏
Keywords: Kaposi's sarcoma-associated herpesvirus
Primary effusion lymphoma
FIT-039
Cyclin-dependent kinase 9
BCBL-1 xenograft
Issue Date: 20-Jan-2023
Publisher: Springer Nature
BMC
Journal title: BMC Cancer
Volume: 23
Thesis number: 71
Abstract: Chronic infection with Kaposi’s sarcoma-associated herpes virus (KSHV) in B lymphocytes causes primary effusion lymphoma (PEL), the most aggressive form of KSHV-related cancer, which is resistant to conventional chemotherapy. In this study, we report that the BCBL-1 KSHV⁺ PEL cell line does not harbor oncogenic mutations responsible for its aggressive malignancy. Assuming that KSHV viral oncogenes play crucial roles in PEL proliferation, we examined the effect of cyclin-dependent kinase 9 (CDK9) inhibitor FIT-039 on KSHV viral gene expression and KSHV⁺ PEL proliferation. We found that FIT-039 treatment impaired the proliferation of KSHV⁺ PEL cells and the expression of KSHV viral genes in vitro. The effects of FIT-039 treatment on PEL cells were further evaluated in the PEL xenograft model that retains a more physiological environment for the growth of PEL growth and KSHV propagation, and we confirmed that FIT-039 administration drastically inhibited PEL growth in vivo. Our current study indicates that FIT-039 is a potential new anticancer drug targeting KSHV for PEL patients.
Rights: © The Author(s) 2023
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
URI: http://hdl.handle.net/2433/287059
DOI(Published Version): 10.1186/s12885-023-10540-y
PubMed ID: 36670405
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