A Tale of Two Cell Lines: Characterization of differential efficacy of small molecule drugs cediranib and NU-7441 on primary vs. metastatic colorectal cancer

Abstract

Colorectal cancer is recognized as one of the leading causes of cancer death amongst both sexes in the U.S. Despite rigorous screening, those diagnosed with colon cancer often face poor prognosis, and approximately 70% of affected patients will develop metastatic relapse. The investigation of colon carcinoma cell lines genetic variability and response to chemotherapy panels may aid in targeting therapies to improve outcomes. This study aims to find correlations between metastasis status, gene variability, and drug response. We used two cell lines that were isolated from the same 51-year-old male with colorectal adenocarcinoma: a primary tumor-derived line (SW480) and a secondary metastasis-derived line (SW620). Live cell imaging using time-lapse microscopy over three days exhibited differential cell death responses following treatment with multiple chemotherapeutic agents, particularly cediranib and Nu-7441, with SW620 demonstrating greater sensitivity. Western blots revealed changes in DNA repair machinery expression (particularly NHEJ proteins) between SW480 and SW620. RNA sequencing and Gene Ontology analysis corroborated our findings, demonstrating upregulated DNA repair and metabolic survival genes including TGM2 in SW620 and PROM1 in SW480. An SW620 line grown in non-attachment plates and then reattached (SW620F) exhibited high DNA-PKcs activation and drug sensitivity. Correlation between drug response and gene expression crucial to cell growth and successful metastasis may reveal new biomarkers to target potential treatments.