Application of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10540-y |
| _version_ | 1797945882037977088 |
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| author | Tetsunori Sakamoto Masahiko Ajiro Akira Watanabe Shingo Matsushima Keiji Ueda Masatoshi Hagiwara |
| author_facet | Tetsunori Sakamoto Masahiko Ajiro Akira Watanabe Shingo Matsushima Keiji Ueda Masatoshi Hagiwara |
| author_sort | Tetsunori Sakamoto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T21:02:10Z |
| format | Article |
| id | doaj.art-701bb42d15e14b0bb1dcd3d489a90632 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-10T21:02:10Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-701bb42d15e14b0bb1dcd3d489a906322023-01-22T12:16:29ZengBMCBMC Cancer1471-24072023-01-0123111210.1186/s12885-023-10540-yApplication of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancyTetsunori Sakamoto0Masahiko Ajiro1Akira Watanabe2Shingo Matsushima3Keiji Ueda4Masatoshi Hagiwara5Department of Anatomy and Developmental Biology, Kyoto University Graduate School of MedicineDepartment of Anatomy and Developmental Biology, Kyoto University Graduate School of MedicineMedical Innovation Center, Kyoto University Graduate School of MedicineDepartment of Drug Discovery Medicine, Kyoto University Graduate School of MedicineDivision of Virology, Osaka University Graduate School of MedicineDepartment of Anatomy and Developmental Biology, Kyoto University Graduate School of MedicineAbstract 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.https://doi.org/10.1186/s12885-023-10540-yKaposi’s sarcoma-associated herpesvirusPrimary effusion lymphomaFIT-039Cyclin-dependent kinase 9BCBL-1 xenograft |
| spellingShingle | Tetsunori Sakamoto Masahiko Ajiro Akira Watanabe Shingo Matsushima Keiji Ueda Masatoshi Hagiwara Application of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy BMC Cancer Kaposi’s sarcoma-associated herpesvirus Primary effusion lymphoma FIT-039 Cyclin-dependent kinase 9 BCBL-1 xenograft |
| title | Application of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy |
| title_full | Application of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy |
| title_fullStr | Application of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy |
| title_full_unstemmed | Application of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy |
| title_short | Application of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy |
| title_sort | application of the cdk9 inhibitor fit 039 for the treatment of kshv associated malignancy |
| topic | Kaposi’s sarcoma-associated herpesvirus Primary effusion lymphoma FIT-039 Cyclin-dependent kinase 9 BCBL-1 xenograft |
| url | https://doi.org/10.1186/s12885-023-10540-y |
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