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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 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.

SUBMITTER: Zong Y

PROVIDER: S-EPMC10973306 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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

Zong Yi Y Tao Zhigang Z Jiang Siyi S Wang Minyuan M Yu Weihua W

Discover oncology 20240328 1

<h4>Background/aim</h4>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.<h4>Materials and methods</h4>We performed high-throughput drug screening in combination with Lenvatinib. And we employed CCK-8-based Bliss Synergy Score analysis, colony formation and w ...[more]

PMID: 38538885

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