Direct comparison of efficacy of combining ivermectin versus five first-line chemotherapy drugs with recombinant methioninase against colon-cancer cells.

Authors

Jinsoo Kim, Qinghong Han, Shukuan Li, Byung Mo Kang, Yuta Miyashi, Tomoyuki Ishiguro, Michael Bouvet, Robert M Hoffman

Published in

Frontiers in oncology. Volume 16. Pages 1807785. Epub Jun 03, 2026.

Abstract

Ivermectin is emerging as a potential anticancer agent. Recombinant methioninase (rMETase) targets methionine addiction of cancer and shows synergistic efficacy when combined with cancer-chemotherapy drugs. In the present study, we compared the efficacy of the rMETase combination with ivermectin versus rMETase combined with each of five first-line chemotherapeutic agents, on HCT116 human colon-cancer cells.
The half-maximal inhibitory concentrations (IC₅₀) of rMETase, ivermectin, and five first-line chemotherapy drugs were determined from dose-response curves. HCT116 colon-cancer cells were then treated with each drug at its IC₅₀ concentration, either alone, or in combination with rMETase, at their IC₅₀ concentration. Cell viability was assessed after 72 h using the WST-8 assay. A chemosensitivity index (CI) was defined as the ratio of cancer-cell viability after treatment with each drug alone at its IC₅₀ to that after treatment with the same drug at its IC₅₀ concentration combined with rMETase.
At the IC₅₀ concentration, ivermectin combined with rMETase (CI, 6.7 ± 1.9) was significantly (p < 0.05) more effective than rMETase combined with 5-fluorouracil (CI, 2.0 ± 0.7); cisplatinum (CI, 2.4 ± 1.5); gemcitabine (CI, 2.5 ± 0.7); and paclitaxel (CI, 2.8 ± 0.5). Only doxorubicin combined with rMETase was slightly more effective than rMETase combined with ivermectin (CI, 7.8 ± 1.7).
Ivermectin combined with rMETase was more effective than four of five first-line chemotherapy drugs combined with rMETase against colon-cancer cells, demonstrating additional promise of ivermectin as an anticancer drug.

PMID:
42318457
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.

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