Title:SHR6390 Combined with Cabozantinib Inhibits Tumor Progression in the
Hepatocellular Carcinoma Mouse Model
Volume: 24
Issue: 5
Author(s): Caiqi Liu, Jiaqi Shi, Binlin Lin, Meng Zhou, Dan Shan, Jianhua Nie, Yan Wang, Yanqiao Zhang, Peng Han*Tongsen Zheng*
Affiliation:
- Department of General Surgery, the First Affiliated Hospital
of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang,
People's Republic of China
- Key Laboratory of Molecular Oncology of Heilongjiang Province, Harbin,
Heilongjiang, People's Republic of China
- Department of Phase 1 Trials
Center, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People's Republic of China
- Key Laboratory
of Molecular Oncology, Heilongjiang Cancer Institute, Harbin, People's Republic of China
Keywords:
SHR6390, cabozantinib, Rb, c-Met, combination therapy, hepatocellular carcinoma, liver cancer.
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.
