Current Gene TherapyCurrent Gene TherapyCurrent Gene Therapy1566-52321875-5631Bentham Science64408210.2174/1566523222666220825110147Life SciencesResearch ArticleSHR6390 Combined with Cabozantinib Inhibits Tumor Progression in the Hepatocellular Carcinoma Mouse ModelLiuCaiqiinfo@benthamscience.netHanPenginfo@benthamscience.netZhangYanqiaoinfo@benthamscience.netWangYaninfo@benthamscience.netNieJianhuainfo@benthamscience.netShanDaninfo@benthamscience.netZhouMenginfo@benthamscience.netLinBinlininfo@benthamscience.netShiJiaqiinfo@benthamscience.netZhengTongseninfo@benthamscience.netDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer HospitalDepartment of General Surgery, the First Affiliated Hospital of Harbin Medical UniversityDepartment of Colorectal Surgery, Harbin Medical University Cancer Hospital0105202424545346407012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://journals.eco-vector.com/1566-5232/article/view/644082

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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