SHR6390 Combined with Cabozantinib Inhibits Tumor Progression in the Hepatocellular Carcinoma Mouse Model
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Updated: Aug 30, 2025
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Caiqi Liu1,2, Jiaqi Shi1,2, Binlin Lin1
1Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People's Republic of China.
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.
Insights
The novel CDK4/6 inhibitor SHR6390 shows anti-tumor effects in hepatocellular carcinoma (HCC). Combination therapy with cabozantinib enhances SHR6390's efficacy, offering a promising strategy for HCC treatment.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Hepatocellular carcinoma (HCC) remains a significant health challenge.
- The efficacy of the novel CDK4/6 inhibitor SHR6390 in HCC is currently unknown.
Purpose of the Study:
- To investigate the combined therapeutic effect of SHR6390 and cabozantinib in HCC.
- To elucidate the antitumor mechanisms of this combination therapy for HCC patients.
Main Methods:
- Cell Counting Kit 8 (CCK8), wound healing, and Transwell assays were used to assess cell viability, migration, and invasion.
- Western blotting and immunohistochemistry were employed to analyze molecular mechanisms.
- A subcutaneous HCC tumor mouse model was utilized to evaluate in vivo efficacy.
Main Results:
- SHR6390 demonstrated potent, dose-dependent anti-proliferative activity against HCC cells.
- The combination of SHR6390 and cabozantinib significantly enhanced inhibition of cell viability, migration, and invasion compared to monotherapy.
- SHR6390 monotherapy and the combination therapy showed synergistic antitumor activity in vivo, with SHR6390 reducing Rb phosphorylation.
Conclusions:
- SHR6390 exhibits significant efficacy as a monotherapy or in combination with cabozantinib for treating HCC.
- This combination therapy presents a potentially more effective therapeutic strategy for HCC patients.
