Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib

被引：0

作者：

Zong, Yi ^{[2
]}

Tao, Zhigang ^{[3
]}

Jiang, Siyi ^{[4
]}

Wang, Minyuan ^{[2
]}

Yu, Weihua ^{[1
]}

机构：

[1] Zhejiang Univ, Sch Med, Affiliated Hosp 4, Dept Gastroenterol, Yiwu, Zhejiang, Peoples R China

[2] Zhejiang Univ, Affiliated Hosp 4, Sch Med, Dept Radiol, Yiwu, Zhejiang, Peoples R China

[3] Hangzhou Canc Hosp, Dept Radiol, Hangzhou, Zhejiang, Peoples R China

[4] Zhejiang Univ, Affiliated Hosp 4, Sch Med, Intens Care Unit, Yiwu, Zhejiang, Peoples R China

来源：

DISCOVER ONCOLOGY | 2024年 / 15卷 / 01期

关键词：

Lenvatinib; Lysine specific demethylase 1; Liver cancer; Epigenetic dysregulation; PI3K; PHASE-II; HEPATOCELLULAR-CARCINOMA; SORAFENIB; RECURRENT; THERAPY;

D O I：

10.1007/s12672-024-00947-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：8

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