Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase

• Published in: Chinese journal of integrative medicine 2024-06, Vol.30 (6), p.499-506
• Main Authors: Li, Qi, Kong, Zhao-di, Wang, Huan, Gu, Hong-hui, Chen, Zhong, Li, Shi-guang, Chen, Yi-qi, Cai, Yu, Yang, Zhen-jiang
• Format: Article
• Language: English
• Subjects: Animals; Body Weight - drug effects; Cachexia - drug therapy; Cachexia - pathology; Cell Line, Tumor; Colonic Neoplasms - complications; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Male; Medicine; Medicine & Public Health; Medroxyprogesterone Acetate - pharmacology; Mice; Mice, Inbred BALB C; Muscular Atrophy - drug therapy; Muscular Atrophy - pathology; Original Article; STAT3 Transcription Factor - metabolism; Ubiquitin-Protein Ligases - metabolism
• ISSN: 1672-0415; 1993-0402
• DOI: 10.1007/s11655-023-3702-4

Objective To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia. Methods A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg −1 •d −1 ), MPA + low-dose (20 mg•kg −1 •d −1 ) JP (L-JP), MPA + medium-dose (30 mg•kg −1 •d −1 ) JP (M-JP), and MPA + high-dose (40 mg•kg −1 •d −1 ) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase. Results JP combined with MPA restored tumor-induced weight loss ( P