Evaluation of AMG510 Therapy on KRAS -Mutant Non-Small Cell Lung Cancer and Colorectal Cancer Cell Using a 3D Invasive Tumor Spheroid System under Normoxia and Hypoxia

• Published in: Bioengineering (Basel) Vol. 9; no. 12; p. 792
• Main Authors: Huang, Meng, Hou, Wei, Zhang, Jing, Li, Menglan, Zhang, Zilin, Li, Xiaoran, Chen, Zaozao, Wang, Cailian, Yang, Lihua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-12-2022; MDPI
• Subjects: AMG510; Artificial intelligence; Bioengineering; Cell culture; Cell growth; Cell viability; Colorectal cancer; Colorectal carcinoma; Computed tomography; Environmental chambers; Evaluation; Extracellular matrix; Gene expression; Hydrogels; Hypoxia; imaging; In vitro methods and tests; In vivo methods and tests; invasion; Invasiveness; K-Ras protein; KRAS; Lung cancer; Microenvironments; Mutants; Non-small cell lung carcinoma; non–small cell lung cancer; Sensitivity analysis; spheroid; Spheroids; Test chambers; Three dimensional models; Tumors; China; AMG510; colorectal cancer; invasion; non–small cell lung cancer; KRAS; imaging; spheroid
• ISSN: 2306-5354; 2306-5354
• DOI: 10.3390/bioengineering9120792

A 3D tumor spheroid has been increasingly applied in pharmaceutical development for its simulation of the tumor structure and microenvironment. The embedded-culture of a tumor spheroid within a hydrogel microenvironment could help to improve the mimicking of in vivo cell growth and the development of 3D models for tumor invasiveness evaluation, which could enhance its drug efficiency prediction together with cell viability detection. NCI-H23 spheroids and CT-26 spheroids, from a non-small cell lung cancer and colorectal cancer cell line, respectively, together with extracellular matrix were generated for evaluating their sensitivity to AMG510 (a
inhibitor) under normoxia and hypoxia conditions, which were created by an on-stage environmental chamber. Results demonstrated that NCI-H23, the
moderate expression cell line, only mildly responded to AMG510 treatment in normal 2D and 3D cultures and could be clearly evaluated by our system in hypoxia conditions, while the negative control CT-26 (
-mutant) spheroid exhibited no significant response to AMG510 treatment. In summary, our system, together with a controlled microenvironment and imaging methodology, provided an easily assessable and effective methodology for 3D in vitro drug efficiency testing and screenings.