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

BACKGROUND/AIM: 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.

MATERIALS AND

METHODS

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.

RESULTS

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).

DISCUSSION: 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.