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Published on: August 2, 2024
Suppression of human epidermal growth factor receptor 2 via interference increases the chemosensitivity of ovarian
Xiaoping Song1, Kailv Sun2, Jianming Hu1
1Division of Gynecology and Obstetrics, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Abstract:
The function of human epidermal growth factor receptor 2 (HER2) in the chemosensitivity of ovarian carcinoma has not been fully investigated, therefore, the present study aimed to analyze the potential role of HER2 in ovarian carcinoma chemosensitivity in further detail. SKOV3 cells were transfected with lentiviral-mediated HER2-small hairpin RNA (shRNA) molecules to establish the stable expression of HER2-shRNA in the SKOV3 cell line (knockdown cells; KD) and negative control cell line (NC). The untransfected SKOV3 cell line served as the blank control (CON) group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect the expression of HER2 in the three different cell types, which were subsequently examined for growth inhibition using a cell counting kit-8 assay. The CON and KD cell strains were utilized to establish xenograft models in nude mice, primarily to detect the expression of the HER2 protein, and additionally to observe tumor size changes under the treatment of cisplatin (DDP) chemotherapy. RT-qPCR and western blot analysis demonstrated a significant decrease in the levels of HER2 mRNA and protein in the KD cells. The suppression of HER2 expression resulted in an increase of chemotherapy sensitivity in the SKOV3 cells. HER2 protein expression decreased significantly following transduction with specific HER2-shRNA. Additionally, growth slowed significantly under treatment with DDP in ovarian cancer transplantation tumors. In conclusion, lentivirus-mediated HER2-shRNA effectively inhibits the expression of the HER2 gene, and increases the chemosensitivity to DDP in ovarian carcinoma.
Insights
This study investigated human epidermal growth factor receptor 2 (HER2) in ovarian cancer. Suppressing HER2 with lentiviral-mediated small hairpin RNA (shRNA) increased chemotherapy sensitivity in ovarian cancer cells and xenografts.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The role of human epidermal growth factor receptor 2 (HER2) in ovarian carcinoma chemosensitivity remains incompletely understood.
- HER2 is a known oncogene implicated in various cancers, but its specific function in ovarian cancer drug response requires further elucidation.
Purpose of the Study:
- To investigate the potential role of HER2 in the chemosensitivity of ovarian carcinoma.
- To determine if inhibiting HER2 expression can enhance the efficacy of chemotherapy in ovarian cancer models.
Main Methods:
- Established stable HER2-knockdown (KD) SKOV3 ovarian cancer cell lines using lentiviral-mediated HER2-small hairpin RNA (shRNA).
- Utilized reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot to confirm HER2 gene and protein suppression.
- Assessed cell growth inhibition using a cell counting kit-8 assay and evaluated tumor growth in xenograft models treated with cisplatin (DDP).
Main Results:
- Lentiviral-mediated HER2-shRNA significantly reduced HER2 mRNA and protein expression in SKOV3 cells (KD group) compared to control groups.
- Suppression of HER2 expression led to increased chemosensitivity in ovarian cancer cells.
- HER2 knockdown resulted in significantly slower tumor growth in vivo when treated with DDP chemotherapy.
Conclusions:
- Lentivirus-mediated HER2-shRNA is an effective method for inhibiting HER2 gene expression in ovarian carcinoma.
- Inhibiting HER2 expression enhances the chemosensitivity of ovarian cancer to cisplatin (DDP).
- Targeting HER2 represents a potential therapeutic strategy to improve ovarian cancer treatment outcomes.
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