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Shepherdin Affects the Biological Behavior of Rhabdomyosarcoma and Enhances its X-Ray Sensitivity
Li Niu1, Mei Kang1, Menghuan Yao2
1Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
Abstract:
Shepherdin, a specific inhibitor of survivin, is widely used to suppress tumor growth. However, there is little research on whether shepherdin also regulates other biological behaviors of rhabdomyosarcoma (RMS) cells. Therefore, in our study, we aimed to explore the potential role of shepherdin in RMS cells. Our findings demonstrated that shepherdin significantly influences RMS cell growth, alters the cytoskeleton, and disrupts the cell cycle progression. Specifically, shepherdin downregulates FAK expression, leading to cytoskeleton disruption and cell cycle arrest at the G0/G1 and G2/M phases. Furthermore, our subsequent results indicated that both shepherdin treatment and survivin knockdown enhanced the sensitivity of RMS to X-ray irradiation both in vivo and in vitro. This phenomenon was evidenced by the following indicators: reduced clone formation, increased cell apoptosis, cell cycle arrest, as well as the inhibition of tumor cell proliferation. Taken together, our study revealed that shepherdin not only modulates the biological behavior of RMS cells but also enhances their sensitivity to X-ray irradiation, demonstrating its potential as an effective therapeutic strategy for RMS.
Insights
Shepherdin, a survivin inhibitor, impacts rhabdomyosarcoma cell growth and cycle. It also sensitizes these cells to X-ray irradiation, showing therapeutic potential for rhabdomyosarcoma.
Area of Science:
- Oncology
- Cell Biology
Background:
- Shepherdin is a survivin inhibitor used for tumor suppression.
- Limited research exists on shepherdin's effects on rhabdomyosarcoma (RMS) cell behaviors beyond tumor growth.
Purpose of the Study:
- To investigate the role of shepherdin in regulating RMS cell biological behaviors.
- To explore shepherdin's impact on RMS cell growth, cytoskeleton, and cell cycle.
- To assess shepherdin's potential to enhance RMS sensitivity to X-ray irradiation.
Main Methods:
- Treatment of RMS cells with shepherdin.
- Analysis of RMS cell growth, cytoskeleton, and cell cycle progression.
- Evaluation of FAK (Focal Adhesion Kinase) expression.
- Assessment of RMS sensitivity to X-ray irradiation in vitro and in vivo.
- Survivin knockdown experiments.
Main Results:
- Shepherdin significantly affects RMS cell growth, cytoskeleton, and cell cycle progression.
- Shepherdin downregulates FAK expression, causing cytoskeleton disruption and G0/G1 and G2/M phase cell cycle arrest.
- Both shepherdin treatment and survivin knockdown increased RMS sensitivity to X-ray irradiation.
- Enhanced radiosensitivity was indicated by reduced clone formation, increased apoptosis, cell cycle arrest, and inhibited proliferation.
Conclusions:
- Shepherdin modulates RMS cell biological behavior, including growth, cytoskeleton, and cell cycle.
- Shepherdin enhances the radiosensitivity of rhabdomyosarcoma cells.
- Shepherdin presents a potential therapeutic strategy for rhabdomyosarcoma, particularly in combination with X-ray irradiation.
