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Silencing stathmin-modulating efficiency of chemotherapy for esophageal squamous cell cancer with paclitaxel
1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Abstract:
Paclitaxel (PTX) is broadly considered the drug of choice for treating human esophageal squamous cell cancer (ESCC). However, PTX resistance often ultimately leads to treatment failure. stathmin, or Op18, is a ubiquitously expressed 19-kDa cytosolic phosphoprotein that can integrate various cellular regulatory signals. stathmin overexpression could lead to resistance to chemotherapeutic agents. In this study we investigated the effect of stathmin gene silencing, using small interfering RNA (stathmin siRNA), on the efficacy of PTX in ESCC. Transfection of stathmin siRNA could significantly inhibit stathmin mRNA and protein levels in ESCC cell lines EC9706 and Eca-109. The silencing of stathmin combined with PTX significantly inhibited the proliferation of EC9706 and Eca-109 cells, with a significantly higher proportion of cells at G2/M phase and this antiproliferative effect was accompanied by an increase in apoptosis rates and morphology changes of EC9706 and Eca-109. Thus, combined chemotherapeutic agent PTX and stathmin siRNA could potentially enhance the therapeutic outcomes of PTX in treating ESCC.
Insights
Paclitaxel resistance in esophageal cancer is a major challenge. Silencing the stathmin gene with siRNA enhances paclitaxel
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Paclitaxel (PTX) is a primary treatment for esophageal squamous cell cancer (ESCC).
- Drug resistance, particularly to PTX, frequently leads to treatment failure in ESCC.
- Stathmin overexpression is linked to chemoresistance in various cancers.
Purpose of the Study:
- To investigate the impact of stathmin gene silencing on the efficacy of PTX in ESCC.
- To evaluate the potential of combining PTX with stathmin siRNA for improved ESCC treatment.
Main Methods:
- Utilized small interfering RNA (siRNA) to silence the stathmin gene in ESCC cell lines (EC9706 and Eca-109).
- Assessed the effects of stathmin gene silencing alone and in combination with PTX on cell proliferation, cell cycle progression, and apoptosis.
- Measured stathmin mRNA and protein levels following siRNA transfection.
Main Results:
- Stathmin siRNA effectively reduced stathmin mRNA and protein expression in ESCC cell lines.
- Combined treatment with PTX and stathmin siRNA significantly inhibited ESCC cell proliferation.
- The combination therapy led to a higher proportion of cells in the G2/M phase, increased apoptosis, and observable morphological changes.
Conclusions:
- Stathmin gene silencing can overcome PTX resistance in ESCC.
- Combining PTX with stathmin siRNA demonstrates potential as an enhanced therapeutic strategy for ESCC.
- Targeting stathmin offers a promising approach to improve the clinical outcomes of PTX chemotherapy in ESCC.
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