Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib.
Discov Oncol
; 15(1): 89, 2024 Mar 28.
Article
in En
| MEDLINE
| ID: mdl-38538885
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 ANDMETHODS:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Discov Oncol
Year:
2024
Document type:
Article