Inhibition of heat shock protein (HSP) 90 reverses signal transducer and activator of transcription (STAT) 3‐mediated muscle wasting in cancer cachexia mice

• DOI: 10.1111/bph.15625
• Publication Date: 2021-07-15T19:35:57Z
• Authors: Mengyuan Niu; Shiyu Song; Zhonglan Su; Lulu Wei; Li Li; Wenyuan Pu; Chen Zhao; Yibing Ding; Jinglin Wang; Wangsen Cao; Qian Gao; Hongwei Wang
• Keywords: Muscle Atrophy; FOXO1; C2C12

Background and Purpose Cancer cachexia is a common cause of death among cancer patients with no currently effective treatment available. In animal models, aberrant activation STAT3 in skeletal muscle contributes to wasting. However, clinically the factors regulating molecular mechanisms involved remain incompletely understood. Experimental Approach The expression HSP90 were detected from or tumour‐bearing cachectic mice. inhibitors, including 17DMAG (alvespimycin) PU‐H71, administered cachexic mice parameters, weight loss, food intake, survival rate, body composition, serum metabolites, wasting pathology catabolic analysed. co‐culture C2C12 myotube cells C26 conditioned media was performed investigate pathological mechanism roles HSP90, FOXO1 atrophy explored via overexpression knockdown. Results An enhanced interaction between activated patients, crucial for development inhibitors PU‐H71 alleviated models induced by conditional medium. Prolonged transactivated binding directly its promoter triggered FOXO1‐dependent manner cells. Conclusion Implications HSP90/STAT3/FOXO1 axis plays critical role wasting, which might be potential therapeutic target cachexia.