Fungal immunomodulatory proteins alleviate docetaxel-induced adverse effects

Abstract

Docetaxel is widely used in the treatment of non-small cell lung cancer. Fungal immunomodulatory proteins of Flammulina velutipes (FIP-fve) and Ganoderma tsugae (FIP-gts) possess immunomodulatory and anti-cancer effects. The abilities of FIP-fve and FIP-gts to protect against docetaxel-induced adverse effects were investigated. FIP-gts, but not FIP-fve, reversed docetaxel-induced decrease in white blood cells (WBCs). On haematoxylin and eosin (H & E), FIP-fve and FIP-gts reduced docetaxel-induced empty vacuoles in bone marrow and damage to small intestinal mucosa. On 3D micro-CT analysis, FIP-fve and FIP-gts significantly reversed docetaxel-induced decreases in percent bone volume (BV/TV), trabecular number (Tb.N) and bone surface density (BS/TV) in mice. Moreover, monocyte chemoattractant protein-1 (MCP-1) production and mRNA expressions induced by docetaxel in A549 cells were diminished by FIP-fve and FIP-gts. Thus, FIP-fve and FIP-gts have the potential to mitigate docetaxel-induced adverse effects in patients undergoing chemotherapy and to serve as novel therapeutic protective agents.

Keywords

• Docetaxel
• Fungal immunomodulatory proteins (FIPs)
• Bone microarchitecture
• G-CSF
• Myelotoxicity
• Metastases