The transcription factor NF-kB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-kB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation.

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Our results indicated that ivermectin at its very low dose, which did not induce obvious cytotoxicity, drastically reversed the resistance of the tumor cells to the chemotherapeutic drugs both in vitro and in vivo.

Mechanistically, ivermectin reversed the resistance mainly by reducing the expression of P-glycoprotein (P-gp) via inhibiting the epidermal growth factor receptor (EGFR), not by directly inhibiting P-gp activity. Ivermectin bound with the extracellular domain of EGFR, which inhibited the activation of EGFR and its downstream signaling cascade ERK/Akt/NF-kB. The inhibition of the transcriptional factor NF-kB led to the reduced P-gp transcription.

pubmed.ncbi.nlm.nih.gov