Cathepsin S silencing induces apoptosis of human hepatocellular carcinoma cells
Xuedi Wang1, Li Xiong2, Guotang Yu1
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University Nanning, 530021, China.
Abstract:
This study was to investigate the potential molecular mechanisms underlying the Cathepsin S (CTSS) silencing induced apoptosis of Hepatocellular Carcinoma (HCC) cells with lentivirus-mediated RNA interference. Real-time quantitative PCR and western blot assay were performed to detect the mRNA and protein expression of CTSS, respectively, in 13 HCC cell lines with different metastatic potentials. Results showed MHCC97-H cells had the highest CTSS expression. Therefore, MHCC97-H cells were used in following experiments. Then, lentivirus-mediated RNAi was employed to silence CTSS expression (shCTSS). Annexin V/FITC staining showed NF-κB was activated in shCTSS cells treated with conditioned medium from shCTSS-PAR2 cells. This implies a probable positive correlation between PAR2 and CTSS. In addition, results demonstrated CTSS induced apoptosis of HCC cells and increased their chemosensitivity via regulating NF-κB and activating cleaved caspase-3. Our results indicate that CTSS silencing by lentivirus mediated RNAi can significantly induce apoptosis and chemosensitivity of MHCC97-H cells. This provides an attractive anti-cancer strategy and a novel strategy for the treatment of human HCC.
Insights
Silencing Cathepsin S (CTSS) in liver cancer cells induced apoptosis and increased chemosensitivity. This lentivirus-mediated RNA interference offers a potential anti-cancer strategy for Hepatocellular Carcinoma (HCC) treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular Carcinoma (HCC) is a prevalent cancer with limited treatment options.
- Understanding the molecular mechanisms of HCC progression and cell death is crucial for developing novel therapies.
- Cathepsin S (CTSS) has been implicated in various cellular processes, but its role in HCC requires further elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms by which Cathepsin S (CTSS) silencing induces apoptosis in Hepatocellular Carcinoma (HCC) cells.
- To evaluate the potential of CTSS silencing as an anti-cancer strategy for HCC treatment.
Main Methods:
- Lentivirus-mediated RNA interference was used to silence CTSS expression in HCC cell lines.
- Real-time quantitative PCR and western blot assays were performed to measure CTSS mRNA and protein levels.
- Annexin V/FITC staining and cleaved caspase-3 assays were employed to assess apoptosis and related pathways.
Main Results:
- MHCC97-H cells exhibited the highest CTSS expression and were used for subsequent experiments.
- CTSS silencing (shCTSS) led to significant induction of apoptosis in HCC cells.
- CTSS silencing increased HCC cell chemosensitivity, potentially via regulation of NF-κB and activation of cleaved caspase-3.
- A positive correlation between Protease-Activated Receptor 2 (PAR2) and CTSS was suggested.
Conclusions:
- CTSS silencing via lentivirus-mediated RNAi is an effective strategy to induce apoptosis and enhance chemosensitivity in HCC cells.
- Targeting CTSS presents a promising novel therapeutic approach for human HCC.
- The findings provide a foundation for developing new anti-cancer strategies against liver cancer.
