Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib
Abstract Background/Aim Lenvatinib, a multikinase inhibitor, has become a second-line treatment option for unresectable liver cancer, while its monotherapy response rate is limited. Hence, we aim to investigate whether one of the epigenetic inhibitors will be synthetic lethal with Lenvatinib in live...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer
2024-03-01
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| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-024-00947-9 |
| _version_ | 1797233437279518720 |
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| author | Yi Zong Zhigang Tao Siyi Jiang Minyuan Wang Weihua Yu |
| author_facet | Yi Zong Zhigang Tao Siyi Jiang Minyuan Wang Weihua Yu |
| author_sort | Yi Zong |
| collection | DOAJ |
| description | Abstract Background/Aim Lenvatinib, a multikinase inhibitor, has become a second-line treatment option for unresectable liver cancer, while its monotherapy response rate is limited. Hence, we aim to investigate whether one of the epigenetic inhibitors will be synthetic lethal with Lenvatinib in liver cancer cells. Materials and Methods We performed high-throughput drug screening in combination with Lenvatinib. And we employed CCK-8-based Bliss Synergy Score analysis, colony formation and western blotting to confirm our screening results in both HepG2 and HCCC9810 cells. Results We identified that LSD1 inhibitor Pulrodemstat in combination with Lenvatinib dramatically suppressed the PI3K-AKT signaling and induced a more significant activation of Caspase3 compared to Lenvatinib monotherapy. Conclusion Pulrodemstat synergized with Lenvatinib based on suppression of PI3K-AKT signaling and activation of apoptotic signaling. |
| first_indexed | 2024-04-24T16:16:09Z |
| format | Article |
| id | doaj.art-0fbfdc4c9ac4466bb935782591efc04a |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-04-24T16:16:09Z |
| publishDate | 2024-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-0fbfdc4c9ac4466bb935782591efc04a2024-03-31T11:24:16ZengSpringerDiscover Oncology2730-60112024-03-011511810.1007/s12672-024-00947-9Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinibYi Zong0Zhigang Tao1Siyi Jiang2Minyuan Wang3Weihua Yu4Department of Radiology, The Fourth Affiliated Hospital Zhejiang University School of MedicineDepartment of Radiology, Hangzhou Cancer HospitalIntensive Care Unit, The Fourth Affiliated Hospital Zhejiang University School of MedicineDepartment of Radiology, The Fourth Affiliated Hospital Zhejiang University School of MedicineDepartment of Gastroenterology, The Fourth Affiliated Hospital, Zhejiang University School of MedicineAbstract Background/Aim Lenvatinib, a multikinase inhibitor, has become a second-line treatment option for unresectable liver cancer, while its monotherapy response rate is limited. Hence, we aim to investigate whether one of the epigenetic inhibitors will be synthetic lethal with Lenvatinib in liver cancer cells. Materials and Methods We performed high-throughput drug screening in combination with Lenvatinib. And we employed CCK-8-based Bliss Synergy Score analysis, colony formation and western blotting to confirm our screening results in both HepG2 and HCCC9810 cells. Results We identified that LSD1 inhibitor Pulrodemstat in combination with Lenvatinib dramatically suppressed the PI3K-AKT signaling and induced a more significant activation of Caspase3 compared to Lenvatinib monotherapy. Conclusion Pulrodemstat synergized with Lenvatinib based on suppression of PI3K-AKT signaling and activation of apoptotic signaling.https://doi.org/10.1007/s12672-024-00947-9LenvatinibLysine specific demethylase 1Liver cancerEpigenetic dysregulationPI3K |
| spellingShingle | Yi Zong Zhigang Tao Siyi Jiang Minyuan Wang Weihua Yu Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib Discover Oncology Lenvatinib Lysine specific demethylase 1 Liver cancer Epigenetic dysregulation PI3K |
| title | Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib |
| title_full | Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib |
| title_fullStr | Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib |
| title_full_unstemmed | Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib |
| title_short | Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib |
| title_sort | repression of lsd1 kdm1a activity improves the response of liver cancer cells to the lenvatinib |
| topic | Lenvatinib Lysine specific demethylase 1 Liver cancer Epigenetic dysregulation PI3K |
| url | https://doi.org/10.1007/s12672-024-00947-9 |
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