Catabolic Effects of Chemotherapy Drugs-Inflammatory Cytokines Combination on Myotubes and Endothelial Cells

Abstract

Chemotherapy-induced muscle atrophy significantly impairs quality of life in cancer patients. While tumor-related inflammation partly explains cachexia-associated wasting, the mechanisms affecting myotubes and endothelial cells remain poorly understood. This thesis examines the catabolic effects of chemotherapy drugs and inflammatory cytokines on C2C12 myotubes and primary skeletal muscle endothelial cells. Myotubes were treated with CPT-11 (20 μg/mL), 5-fluorouracil (50 μg/mL), leucovorin (10 μg/mL), IL-6 (20 ng/mL), and TNF-α (100 ng/mL). Treatment significantly reduced myofibrillar proteins, including MHC-1(−36%), tropomyosin (−65%), and troponin T (−76%), and suppressed anabolic signaling. SNAT1 and LAT1 expression increased by 78% and 127%, respectively. Endothelial cells exposed to the same agents at full and half doses (100% and 50%) for 24 and 48 hours showed heightened stress responses and upregulation of p53 and p21. Partial recovery was observed following treatment removal, though not fully restored. These findings reveal distinct chemotherapy-induced vulnerabilities in muscle and endothelial cells, offering insight into potential therapeutic strategies.