Abstract P108: Colorectal cancer cells grown in vitro as spheroids show a response to the first-line chemotherapy-based combination drug, FOLFOXIRI
Veroniaina Hanitrarimalala, Zdenka Prgomet, My Hedhammar, Anette Gjörloff WingrenAbstract
Background:
Colorectal cancer (CRC) is a major public health concern by being the third most diagnosed and second most lethal cancer globally. Although complete surgical resection of the tumor and its metastatic sites improves overall survival in patients with CRC, approximately 25% of CRC cases are diagnosed at an advanced stage with metastases in distant organs. First-line treatment of metastatic colorectal cancer is the chemotherapy-based combination treatment of 5-fluorouracil (5-FU), folinic acid, oxaliplatin, and/or irinotecan: FOLFOXIRI. Conventional in vitro 3D models, such as spheroids, are unable to recreate the conditions associated with the tumor microenvironment (TME), although it has been shown to have a significant impact on CRC progression and treatment.
Methods:
We treated spheroids from four different CRC cell lines with FOLFOXIRI to monitor the response of the spheroid models. Two primary CRC cell lines were used, HCT116 (KRAS G13D mutation) and HT29 (KRAS WT), and two metastatic cell lines, SW620 and NCI-H508. To better simulate the TME in vitro, we also developed a 3D CRC model supported by a network of the recombinant fibronectin (FN)-silk, which provides a well-defined 3D environment mimicking the natural extracellular matrix (ECM).
Results:
CRC spheroids of HCT116 and NCI-H508 showed a better therapeutic response to FOLFOXIRI treatment than the HT29 and SW620. The HT29 and HCT116 cells grew properly with tumor-like morphology within the 3D FN-silk networks. The H&E staining showed stretched out cells with prominent cytoplasm.
Conclusions:
CRC models based on the FN-silk network allow tumor-like morphology and could be further developed to include co-cultures of fibroblasts and macrophages. Such advanced models could be utilized to study long-term treatment effects and resistance development to conventional drugs in vitro.
Citation Format:
Veroniaina Hanitrarimalala, Zdenka Prgomet, My Hedhammar, Anette Gjörloff Wingren. Colorectal cancer cells grown in vitro as spheroids show a response to the first-line chemotherapy-based combination drug, FOLFOXIRI [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P108.