Luteolin reduces cancer‑induced skeletal and cardiac muscle atrophy in a Lewis lung cancer mouse model.

Abstract

Luteolin was recently demonstrated to suppress tumor growth by interfering with nuclear factor (NF)‑κB activation. As the NF‑κB pathway plays a critical role in muscular atrophy associated with cancer cachexia, we aimed to investigate the potential of luteolin to alleviate cancer‑associated cachexia in a Lewis lung cancer mouse model. C57BL/6 mice were divided into three groups: A control group, a model group and a luteolin group. Mice in the model and luteolin groups received a subcutaneous injection of Lewis lung cancer cells, while the control group received PBS. Subsequently, the tumor mass, serum, gastrocnemius muscle and heart were collected on day21. The serum, gastrocnemius muscle and heart were weighed and prepared for use in enzyme‑linked immunosorbent assay (ELISA), western blotting (WB) and quantitative reverse transcription polymerase chain reaction (qRT‑PCR) analyses. The results revealed that the tumor‑free body mass was significantly reduced in tumor‑bearing mice compared with that of mice in the other groups. The gastrocnemius muscle mass and heart mass were greater in the luteolin treatment group than in the control group. Tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 levels were lower in the luteolin treatment group than in the model group. In addition, according to the results of the WB and qRT‑PCR analyses, the expression of the E3 ubiquitin ligase muscle RING finger‑containing protein1 (MuRF1) was downregulated in skeletal muscle and cardiac muscle, whereas atrogin‑1 was downregulated only in skeletal muscle in the luteolin treatment group vs. the model group. Furthermore, IκB kinaseβ (IKKβ) and phospho‑p65 were significantly downregulated in skeletal muscle and cardiac tissue, whereas the expression of p‑p38 was downregulated only in skeletal muscle in the luteolin treatment group when compared with their expression levels in the model group, as determined by the WB analysis. In conclusion, from the current results, we conclude that luteolin is able to reduce inflammatory burden, downregulate the expression of genes associated with muscle protein breakdown, and protect skeletal and heart muscle from cancer‑induced wasting and loss invivo. Therefore, luteolin has the potential to be developed into a novel anti‑cachetic agent.