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

Meng Huang; Wei Hou; Jing Zhang; Menglan Li; Zilin Zhang; Xiaoran Li; Zaozao Chen; Cailian Wang; Lihua Yang

doi:10.3390/bioengineering9120792

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

Bioengineering (Basel). 2022 Dec 12;9(12):792. doi: 10.3390/bioengineering9120792.

Authors

Meng Huang¹, Wei Hou^{2

3}, Jing Zhang^{4

5}, Menglan Li⁵, Zilin Zhang⁵, Xiaoran Li⁵, Zaozao Chen^{2

4

5}, Cailian Wang^{2

3}, Lihua Yang¹

Affiliations

¹ Medical Center for Digestive Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210009, China.
² State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
³ Department of Oncology, School of Medicine, Southeast University, Nanjing 210009, China.
⁴ Institute of Medical Devices (Suzhou), Southeast University, Suzhou 215163, China.
⁵ Jiangsu Avatarget Biotechnology Co., Ltd., Suzhou 215163, China.

Abstract

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 KRAS^G12C inhibitor) under normoxia and hypoxia conditions, which were created by an on-stage environmental chamber. Results demonstrated that NCI-H23, the KRAS^G12C 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 (G12D-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.

Keywords: AMG510; KRAS; colorectal cancer; imaging; invasion; non–small cell lung cancer; spheroid.

Grants and funding

This work was supported by the National Key R&D Program of China (Grant No. 2017YFA0700500) and Key Project of Jiangsu Commission of Health (K2019030).