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Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Study on the sensitizing effect of SM-1 combined with irradiation on head and neck squamous cell carcinoma
Tong Hu1,2, Gai-Ting Liu1,3, Dan-Dan Wang4
1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin, China.
Purpose:
Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo.
Methods:
MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo.
Results:
In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect.
Conclusion:
SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.
Insights
SM-1 enhances head and neck squamous cell carcinoma (HNSCC) cells' sensitivity to radiation, showing significant anti-tumor effects both in vitro and in vivo. This suggests SM-1 is a promising radiosensitizer for HNSCC clinical trials.
Area of Science:
- Oncology
- Cancer Biology
- Radiotherapy Research
Background:
- Head and neck squamous cell carcinoma (HNSCC) presents a global health challenge with high recurrence rates and poor patient outcomes.
- Current treatment limitations necessitate novel therapeutic strategies to improve HNSCC management.
- SM-1, derived from PAC-1, demonstrates potential by activating procaspase-3 and inducing apoptosis in cancer cells.
Purpose of the Study:
- To investigate the radiosensitizing effect of SM-1 on HNSCC.
- To evaluate the combination therapy of SM-1 and radiation in both in vitro and in vivo models.
- To determine the anti-tumor efficacy and underlying mechanisms of SM-1 as a radiosensitizer for HNSCC.
Main Methods:
- Cell viability assays (MTT) were performed on HNSCC cell lines (HONE1, HSC-2, CAL27).
- Colony formation assays assessed the combined effects of SM-1 and radiation on cell survival.
- Flow cytometry and Western blot analyzed apoptosis, cell cycle, and related protein expression.
- A xenograft tumor model was utilized for in vivo evaluation.
Main Results:
- SM-1 inhibited HNSCC cell activity and synergistically enhanced anti-proliferation with radiation.
- SM-1 significantly increased cancer cell radiosensitivity, outperforming Debio1143.
- SM-1 induced G2/M phase arrest by inhibiting CyclinB1 and CDC2, and promoted apoptosis via caspase-3 activation and PARP1 cleavage.
- In vivo studies confirmed a notable anti-tumor effect of SM-1 combined with irradiation.
Conclusions:
- SM-1 effectively enhances the radiosensitivity of HNSCC cells.
- The findings support SM-1's potential as a clinical radiosensitizer for HNSCC radiotherapy.
- Further clinical trials are warranted to explore SM-1's therapeutic role in HNSCC treatment.
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