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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Slug inhibition increases radiosensitivity of oral squamous cell carcinoma cells by upregulating PUMA
Fangfang Jiang1, Lijie Zhou1, Changbo Wei1
1Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, P.R. China.
Abstract:
As a new strategy, radio-gene therapy was widely used for the treatment of cancer patients in recent few years. Slug was involved in the radioresistance of various cancers and has been found to have an anti-apoptotic effect. This study aims to investigate whether the modulation of Slug expression by siRNA affects oral squamous cell carcinoma sensitivity to X-ray irradiation through upregulating PUMA. Two oral squamous cell carcinoma cell lines (HSC3 and HSC6) were transfected with small interfering RNA (siRNA) targeting Slug and subjected to radiotherapy in vitro. After transfection with Slug siRNA, both HSC3 and HSC6 cells showed relatively lower expression of Slug and higher expression of PUMA. The Slug siRNA transfected cells showed decreased survival and proliferation rates, an increased apoptosis rate and enhanced radiosensitivity to X-ray irradiation. Our results revealed that Slug siRNA transfection in combination with radiation increased the expression of PUMA, which contributed to radiosensitivity of oral squamous cell carcinoma cells. Thus, controlling the expression of Slug might contribute to enhance sensitivity of HSC3 and HSC6 cells toward X-ray irradiation in vitro by upregulating PUMA.
Insights
Modulating Slug expression with siRNA enhances oral cancer cell sensitivity to X-ray radiation by increasing PUMA. This radio-gene therapy approach shows promise for improving cancer treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Radio-gene therapy is an emerging cancer treatment strategy.
- Slug protein is implicated in cancer radioresistance and apoptosis evasion.
- Oral squamous cell carcinoma (OSCC) exhibits radioresistance.
Purpose of the Study:
- To investigate the effect of Slug modulation via siRNA on OSCC radiosensitivity.
- To determine if Slug siRNA influences PUMA expression in OSCC cells.
- To assess the potential of targeting Slug for enhancing radiotherapy efficacy in OSCC.
Main Methods:
- Utilized two OSCC cell lines (HSC3 and HSC6).
- Transfected cells with small interfering RNA (siRNA) targeting Slug.
- Exposed transfected cells to in vitro X-ray irradiation.
- Analyzed Slug and PUMA expression levels.
- Assessed cell survival, proliferation, apoptosis, and radiosensitivity.
Main Results:
- Slug siRNA transfection led to decreased Slug and increased PUMA expression in both cell lines.
- Slug siRNA treatment significantly reduced cell survival and proliferation rates.
- Apoptosis rates were elevated in Slug siRNA-transfected cells.
- Combined Slug siRNA and X-ray irradiation demonstrated enhanced radiosensitivity in OSCC cells.
Conclusions:
- Slug siRNA transfection, combined with radiation, upregulates PUMA expression.
- This upregulation of PUMA contributes to the enhanced radiosensitivity of OSCC cells.
- Controlling Slug expression via siRNA is a potential strategy to improve OSCC sensitivity to X-ray irradiation.
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