WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation

Title:WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation

Volume: 24

Author(s): Anling Chen, Ke Yin, Yu Liu, Lei Hu, Qianwen Cui, Xiaofeng Wan and Wulin Yang*

Affiliation:

• Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China
• Science Island Branch, Graduate School of University of Science and Technology of China, Hefei, 230031, China
• Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230031, China

Abstract: Background: Sorafenib is currently the first choice for the treatment of patients with advanced hepatocellular carcinoma, but its therapeutic effect is still limited.

Objectives: This study aims to examine whether WEE family kinase inhibitors can enhance the anticancer effect of sorafenib.

Methods: We analyzed the expression levels of PKMYT1 kinase and WEE1 kinase in HCC, studied the inhibitory effect of PKMYT1 kinase inhibitor RP-6306, WEE1 kinase inhibitor adavosertib combined with sorafenib on the proliferation of HCC cells, and detected the effect of drug combination on CDK1 phosphorylation.

Results: We found that PKMYT1 and WEE1 were upregulated in HCC and were detrimental to patient survival. Cell experiments showed that both RP-6306 and adavosertib (1-100 μM) inhibited the proliferation of HCC cell lines in a dose-dependent manner alone, and the combination of the two drugs had a synergistic effect. In HCC cell lines, sorafenib combined with RP-6306 or adavosertib showed a synergistic antiproliferation effect and less toxicity to normal cells. Sorafenib combined with RP-6306 and adavosertib further inhibited the proliferation of HCC cells and caused complete dephosphorylation of CDK1.

Conclusion: Taken together, our findings provide experimental evidence for the future use of sorafenib in combination with RP-6306 or adavosertib for the treatment of HCC.

Cite this article as:

Chen Anling, Yin Ke, Liu Yu, Hu Lei, Cui Qianwen, Wan Xiaofeng and Yang Wulin*, WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation, Current Cancer Drug Targets 2024; 24 () . https://dx.doi.org/10.2174/0115680096298370240520093003

DOI https://dx.doi.org/10.2174/0115680096298370240520093003	Print ISSN 1568-0096
Publisher Name Bentham Science Publisher	Online ISSN 1873-5576