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

IF 3.8 4区医学 Q2 GENETICS & HEREDITY

Current gene therapy 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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引用次数: 0

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current gene therapy 医学-遗传学

CiteScore

6.70

自引率

2.80%

发文量

期刊介绍： Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.