1. Radiosensitizing Effect of Trabectedin on Human Soft Tissue Sarcoma Cells.
- Author
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Loi M, Salvatore G, Aquilano M, Greto D, Talamonti C, Salvestrini V, Melica ME, Valzano M, Francolini G, Sottili M, Santini C, Becherini C, Campanacci DA, Mangoni M, and Livi L
- Subjects
- Humans, Trabectedin pharmacology, Trabectedin therapeutic use, Antineoplastic Agents, Alkylating pharmacology, Antineoplastic Agents, Alkylating therapeutic use, Tumor Microenvironment, Radiation-Sensitizing Agents pharmacology, Radiation-Sensitizing Agents therapeutic use, Leiomyosarcoma drug therapy, Sarcoma drug therapy, Sarcoma pathology, Soft Tissue Neoplasms, Liposarcoma drug therapy, Fibrosarcoma, Rhabdomyosarcoma
- Abstract
Trabectedin is used for the treatment of advanced soft tissue sarcomas (STSs). In this study, we evaluated if trabectedin could enhance the efficacy of irradiation (IR) by increasing the intrinsic cell radiosensitivity and modulating tumor micro-environment in fibrosarcoma (HS 93.T), leiomyosarcoma (HS5.T), liposarcoma (SW872), and rhabdomyosarcoma (RD) cell lines. A significant reduction in cell surviving fraction (SF) following trabectedin + IR compared to IR alone was observed in liposarcoma and leiomyosarcoma (enhancement ratio at 50%, ER50: 1.45 and 2.35, respectively), whereas an additive effect was shown in rhabdomyosarcoma and fibrosarcoma. Invasive cells' fraction significantly decreased following trabectedin ± IR compared to IR alone. Differences in cell cycle distribution were observed in leiomyosarcoma and rhabdomyosarcoma treated with trabectedin + IR. In all STS lines, trabectedin + IR resulted in a significantly higher number of γ-H2AX (histone H2AX) foci 30 min compared to the control, trabectedin, or IR alone. Expression of ATM, RAD50, Ang-2, VEGF, and PD-L1 was not significantly altered following trabectedin + IR. In conclusion, trabectedin radiosensitizes STS cells by affecting SF (particularly in leiomyosarcoma and liposarcoma), invasiveness, cell cycle distribution, and γ-H2AX foci formation. Conversely, no synergistic effect was observed on DNA damage repair, neoangiogenesis, and immune system.
- Published
- 2022
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