SHR6390 Combined with Cabozantinib Inhibits Tumor Progression in the Hepatocellular Carcinoma Mouse Model.

IF 4.7 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-01-01 DOI:10.2174/1566523222666220825110147

Caiqi Liu, Jiaqi Shi, Binlin Lin, Meng Zhou, Dan Shan, Jianhua Nie, Yan Wang, Yanqiao Zhang, Peng Han, Tongsen Zheng

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Abstract

Background: A novel CDK4/6 inhibitor SHR6390 has shown significant anti-tumor effects. However, its role in hepatocellular carcinoma (HCC) remains unknown.

Objective: To explore the inhibitory effect of combination treatment with SHR6390 and cabozantinib in HCC, and its antitumor mechanism, so as to provide a more effective therapeutic strategy for HCC patients.

Methods: We investigated SHR6390, monotherapy or combined with cabozantinib, by CCK8, wound healing, transwell, western blotting, immunohistochemistry and mouse model of a subcutaneous tumor.

Results: Our results show that SHR6390 exhibited potent anti-proliferative activity against HCC in a dose-dependent manner. SHR6390 combined with cabozantinib exhibited more potent inhibition of cell viability, migration and invasion. In terms of potential mechanisms, we found that cabozantinib could lead to phosphorylation of Rb, which was reduced in SHR6390 and combined groups. SHR6390 monotherapy inhibited the growth of subcutaneous HCC tumors, besides, the combination treatment with SHR6390 and cabozantinib exerted synergistic anti-tumor activity in vivo Conclusion: SHR6390 is effective against HCC, monotherapy or combined with cabozantinib.

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SHR6390 联合 cabozantinib 可抑制肝细胞癌小鼠模型的肿瘤进展。

背景：一种新型CDK4/6抑制剂SHR6390已显示出显著的抗肿瘤作用。然而，它在肝细胞癌（HCC）中的作用仍然未知：探讨SHR6390与卡博替尼联合治疗对HCC的抑制作用及其抗肿瘤机制，从而为HCC患者提供更有效的治疗策略：我们通过CCK8、伤口愈合、transwell、Western blotting、免疫组化和小鼠皮下肿瘤模型对SHR6390单药治疗或与卡博替尼联合治疗进行了研究：结果：我们的研究结果表明，SHR6390对HCC具有强效的抗增殖活性，且呈剂量依赖性。SHR6390联合卡博替尼对细胞活力、迁移和侵袭有更强的抑制作用。在潜在机制方面，我们发现卡博替尼可导致 Rb 磷酸化，而 SHR6390 和联合治疗组的 Rb 磷酸化程度降低。SHR6390单药治疗可抑制皮下HCC肿瘤的生长，而SHR6390与卡博替尼联合治疗则可在体内发挥协同抗肿瘤活性：结论：无论是单药治疗还是与卡博替尼联合治疗，SHR6390都能有效抗击HCC。

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567

期刊介绍： ACS Applied Electronic Materials is an interdisciplinary journal publishing original research covering all aspects of electronic materials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials science, engineering, optics, physics, and chemistry into important applications of electronic materials. Sample research topics that span the journal's scope are inorganic, organic, ionic and polymeric materials with properties that include conducting, semiconducting, superconducting, insulating, dielectric, magnetic, optoelectronic, piezoelectric, ferroelectric and thermoelectric. Indexed/Abstracted： Web of Science SCIE Scopus CAS INSPEC Portico

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