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Updated: Jan 30, 2026
Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration
Published on: May 31, 2018
GSK923295 as a potential antihepatocellular carcinoma agent causing delay on liver regeneration after partial
Jia-Cheng Tang1, Ke Wu, Xing Zheng
1Key Laboratory of Endoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, China.
Background:
The clinical trials emerged centromere protein E inhibitor GSK923295 as a promising anticancer drug, but its function in hepatocellular carcinoma (HCC) remain needs to be fully elucidated, especially as chemotherapy after hepatectomy for liver tumors. We aimed to describe anti-HCC activities of GSK923295 and compare its antiproliferative effects on liver regeneration after partial hepatectomy (PH).
Methods:
All subjects were randomized to treatment with either vehicle or GSK923295. Antitumor activity of GSK923295 was assessed by xenograft growth assays. The C57BL/6 mice were subjected to 70% PH and the proliferation was calculated by liver coefficient, further confirmed by immunohistochemistry. The proliferation and cell cycle analysis of liver cell AML12 and HCC cells LM3, HUH7, and HepG2 were investigated using the cell counting kit-8 assay and Flow Cytometry. The chromosome misalignment and segregation in AML12 cells were visualized by immunofluorescence.
Results:
Treatment with GSK923295 induced antiproliferation in HCC cell lines. It also caused delay on HCC tumor growth instead of regression both in a HCC cell line xenograft model and patient-derived tumor xenograft model. With microarray analysis, CENtromere Protein E was gradually increased in mouse liver after PH. Exposure of liver cells to GSK923295 resulted in delay on a cell cycle in mitosis with a phenotype of misaligned chromosomes and chromosomes clustered. In 70% PH mouse model, GSK923295 treatment also remarkably reduced liver regeneration in later stage, in parallel with the mitotic marker phospho-histone H3 elevation.
Conclusion:
The anticancer drug GSK923295 causes a significant delay on HCC tumor growth and liver regeneration after PH in later stage.
Insights
The anticancer drug GSK923295 inhibits hepatocellular carcinoma (HCC) growth and delays liver regeneration after partial hepatectomy (PH). This study elucidates its effects on HCC and liver repair mechanisms.
Area of Science:
- Oncology
- Hepatology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) remains a significant health concern, necessitating novel therapeutic strategies.
- Centromere protein E (CENPE) inhibitor GSK923295 shows promise as an anticancer agent, but its specific role in HCC and post-hepatectomy liver regeneration requires further investigation.
- Understanding GSK923295's effects is crucial for its potential application as chemotherapy following liver tumor resection.
Purpose of the Study:
- To investigate the anti-HCC activities of GSK923295.
- To evaluate the antiproliferative effects of GSK923295 on liver regeneration subsequent to partial hepatectomy (PH).
- To elucidate the mechanisms underlying GSK923295's action in HCC and liver tissue.
Main Methods:
- Antitumor activity was assessed using xenograft growth assays in HCC cell lines and patient-derived tumor models.
- Mice underwent 70% partial hepatectomy (PH); liver regeneration was quantified by liver coefficient and confirmed via immunohistochemistry.
- Cell proliferation, cell cycle progression, chromosome alignment, and segregation were analyzed in liver and HCC cells using cell counting kit-8, Flow Cytometry, and immunofluorescence.
Main Results:
- GSK923295 demonstrated antiproliferative effects on HCC cell lines and delayed tumor growth in both cell line and patient-derived xenograft models.
- Microarray analysis revealed increased Centromere Protein E expression in mouse liver post-PH.
- GSK923295 exposure in liver cells caused mitotic cell cycle delay with chromosome misalignment and clustering, and significantly reduced liver regeneration in a PH mouse model, correlating with elevated phospho-histone H3.
Conclusions:
- The anticancer drug GSK923295 effectively inhibits HCC cell proliferation and delays tumor growth.
- GSK923295 treatment significantly impairs liver regeneration in the later stages following partial hepatectomy (PH).
- These findings highlight GSK923295's dual role in suppressing HCC and affecting liver repair, suggesting careful consideration for its use in post-surgical settings.
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