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High-Throughput 3D Tumor Spheroid Array Platform for Evaluating Sensitivity of Proton-Drug Combinations.
Lee, Dong Woo; Kim, Jung Eun; Lee, Ga-Haeng; Son, Arang; Park, Hee Chul; Oh, Dongryul; Jo, Kwanghyun; Choi, Changhoon.
Afiliación
  • Lee DW; Department of Biomedical Engineering, Konyang University, Daejeon 35365, Korea.
  • Kim JE; Medical & Bio Decision (MBD), Suwon 16229, Korea.
  • Lee GH; Medical & Bio Decision (MBD), Suwon 16229, Korea.
  • Son A; Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, Korea.
  • Park HC; Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, Korea.
  • Oh D; Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, Korea.
  • Jo K; Department of Radiation Oncology, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
  • Choi C; Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, Korea.
Int J Mol Sci ; 23(2)2022 Jan 06.
Article en En | MEDLINE | ID: mdl-35054773
Proton beam therapy (PBT) is a critical treatment modality for head and neck squamous cell carcinoma (HNSCC). However, not much is known about drug combinations that may improve the efficacy of PBT. This study aimed to test the feasibility of a three-dimensional (3D) tumor-spheroid-based high-throughput screening platform that could assess cellular sensitivity against PBT. Spheroids of two HNSCC cell lines-Fadu and Cal27-cultured with a mixture of Matrigel were arrayed on a 384-pillar/well plate, followed by exposure to graded doses of protons or targeted drugs including olaparib at various concentrations. Calcein staining of HNSCC spheroids revealed a dose-dependent decrease in cell viability for proton irradiation or multiple targeted drugs, and provided quantitative data that discriminated the sensitivity between the two HNSCC cell lines. The combined effect of protons and olaparib was assessed by calculating the combination index from the survival rates of 4 × 4 matrices, showing that Cal27 spheroids had greater synergy with olaparib than Fadu spheroids. In contrast, adavosertib did not synergize with protons in both spheroids. Taken together, we demonstrated that the 3D pillar/well array platform was a useful tool that provided rapid, quantitative data for evaluating sensitivity to PBT and drug combinations. Our results further supported that administration of the combination of PBT and olaparib may be an effective treatment strategy for HNSCC patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos de Selección de Medicamentos Antitumorales / Esferoides Celulares / Ensayos Analíticos de Alto Rendimiento / Quimioradioterapia / Terapia de Protones / Carcinoma de Células Escamosas de Cabeza y Cuello Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos de Selección de Medicamentos Antitumorales / Esferoides Celulares / Ensayos Analíticos de Alto Rendimiento / Quimioradioterapia / Terapia de Protones / Carcinoma de Células Escamosas de Cabeza y Cuello Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article Pais de publicación: Suiza