WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation
文献类型：期刊论文
| 作者 | Chen, Anling5,6; Yin, Ke3; Liu, Yu1; Hu, Lei4; Cui, Qianwen5,6; Wan, Xiaofeng3; Yang, Wulin2,3,5,6 |
| 刊名 | CURRENT CANCER DRUG TARGETS
 |
| 出版日期 | 2024-06-10 |
| 关键词 | Sorafenib WEE family kinase RP-6306 adavosertib hepatocellular carcinoma HCC |
| ISSN号 | 1568-0096 |
| DOI | 10.2174/0115680096298370240520093003 |
| 通讯作者 | Yang, Wulin(yangw@cmpt.ac.cn) |
| 英文摘要 | 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 mu M) 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. |
| WOS关键词 | UNRESECTABLE HEPATOCELLULAR-CARCINOMA ; TUMOR PROGRESSION ; PKMYT1 ; CANCER ; RESISTANCE ; ACTIVATION ; AUTOPHAGY ; MYT1 |
| 资助项目 | National Natural Science Foundation of China[81872276] ; Hefei Municipal Natural Science Foundation[2022048] ; Hefei Municipal Natural Science Foundation[2022050] ; Hefei Municipal Natural Science Foundation[2023032] ; Foundation for the Excellent Young Talents Training Program of Hefei Cancer Hospital[YQJH2020010] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:001244680200001 |
| 出版者 | BENTHAM SCIENCE PUBL LTD |
| 资助机构 | National Natural Science Foundation of China ; Hefei Municipal Natural Science Foundation ; Foundation for the Excellent Young Talents Training Program of Hefei Cancer Hospital |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/136242]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Yang, Wulin |
| 作者单位 | 1.Bengbu Med Coll, Sch Life Sci, Bengbu 233000, Peoples R China 2.Chinese Acad Sci, Inst Hlth & Med Technol, Hefei Inst Phys Sci, 350 Shushanhu Rd, Hefei 230031, Anhui, Peoples R China 3.Chinese Acad Sci, Hefei Canc Hosp, Hefei 230031, Peoples R China 4.Wannan Med Coll, Sch Preclin Med, Wuhu 241002, Peoples R China 5.Chinese Acad Sci, Inst Hlth & Med Technol, Hefei Inst Phys Sci, Anhui Prov Key Lab Med Phys & Technol, Hefei 230031, Peoples R China 6.Grad Sch Univ Sci & Technol China, Sci Isl Branch, Hefei 230031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Anling,Yin, Ke,Liu, Yu,et al. WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation[J]. CURRENT CANCER DRUG TARGETS,2024. |
| APA | Chen, Anling.,Yin, Ke.,Liu, Yu.,Hu, Lei.,Cui, Qianwen.,...&Yang, Wulin.(2024).WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation.CURRENT CANCER DRUG TARGETS. |
| MLA | Chen, Anling,et al."WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation".CURRENT CANCER DRUG TARGETS (2024). |
入库方式： OAI收割
来源：合肥物质科学研究院
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