A novel NCI‐H69V small cell lung cancer functional mini‐tumor model for future treatment screening applications

Abstract

Small cell lung cancer (SCLC) is aggressive and despite multiple clinical trials, its standard of care is unchanged for the past three decades. In vitro cancer models are crucial in chemotherapy development, and three‐dimensional (3D) models aim to bridge the gap between two‐dimensional (2D) flat cultures and in vivo testing. Functional 3D spheroids can better represent the in vivo situation and tumor characteristics than 2D models. An NCI‐H69V SCLC mini‐tumor model was developed in a clinostat‐based rotating bioreactor system. Spheroid growth and viability were characterized for 30 days, and the ideal experimental window with mature and metabolically stable spheroids was determined. Application of the model for anticancer treatment screening was validated with the standard chemotherapeutic drug irinotecan, for an exposure period of 72 h. The following parameters were measured: soluble protein content, planar surface area measurements, intracellular adenosine triphosphate and extracellular adenylate kinase levels, and glucose consumption. Histological morphology of the spheroids was observed. The established model proved viable and stable, while treatment with irinotecan caused a decrease in cell growth, viability, and glucose consumption demonstrating reactivity of the model to chemotherapy. Therefore, this NCI‐H69V SCLC functional spheroid model could be used for future anticancer compound screening.

Establishment of a small-cell lung cancer (SCLC) mouse model using enhanced cancer stem-cell-functioning 3D SCLC spheroids

“…However, it has limitations in replicating the natural proliferation, migration, and drug penetration that occur in the 3D environment within the human body. Therefore, the use of 3D models offers advantages in mimicking human-like microenvironments, and for such 3D model research, standardization and uniformity in spheroids are crucial factors [20,24,25,26]. In this study, we achieved uniformity in the size and shape of SCLC spheroids using the SpheroFILM culture platform, and we established culture conditions that can produce > 300 spheroids from a single standardized SpheroFILM culture platform.…”

“…Generally, 2D culture serves as the primary preclinical testing model used in the development and discovery of lung cancer drugs [20,23]. However, it has limitations in replicating the natural proliferation, migration, and drug penetration that occur in the 3D environment within the human body.…”

“…Pluripotency indicators (KLF4, Nanog), cell cycle regulators (CDKN1A, JUNB, MDM2), metastasis-related genes (CD44, THY1, MMP9, SNAIL1), and NOTCH pathway and pathway were explained by 3D cultivation of lung cancer cell lines [19]. In addition, it was con rmed that there was a difference in molecular level compared to when NCI-H23 cells, which are lung cancer cells, were 3D-cultured, explaining the possibility of using them as preclinical testing tools to reduce high drug attrition rates [20]. In vivo studies using 3D culture models are also being conducted by other researchers.…”

A Novel NCI-H69AR Drug-Resistant Small-Cell Lung Cancer Mini-Tumor Model for Anti-Cancer Treatment Screening

“…Ascorbic acid plays a role in the folding and deposition of collagen proteins, impacting the extracellular matrix (ECM). A better ECM production improved the structure formation and overall well-being of the spheroids [41]. The SphericalPlate 5D plate was then centrifuged at 1218× g for 5 min to remove air bubbles.…”

Investigation on the incidence and risk factors of lung cancer among Chinese hospital employees

“…8,[12][13][14] From 2002 to 2004, the National Lung Screening Trial (NLST) was carried out by the American Lung Cancer Screening Research Group. 10,[15][16][17] A total of 53 454 people at high risk of lung cancer were included, and they were randomly divided into LDCT group and chest X-ray group. Compared with chest X-ray, LDCT can reduce lung cancer mortality by 20%.…”