High-Throughput 3D Tumor Spheroid Array Platform for Evaluating Sensitivity of Proton-Drug Combinations.

Abstract

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.

• Authors: Dong Woo Lee, Jung Eun Kim, Ga-Haeng Lee, Arang Son, Hee Chul Park, Dongryul Oh, Kwanghyun Jo, Changhoon Choi
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 2 (Jan 06 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35054773 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents

Topics

• Antineoplastic Agents (therapeutic use)
• Cell Line, Tumor
• Chemoradiotherapy
• Drug Screening Assays, Antitumor (methods)
• High-Throughput Screening Assays (methods)
• Humans
• Proton Therapy
• Spheroids, Cellular
• Squamous Cell Carcinoma of Head and Neck (therapy)