Morinaga Sei, Han Qinghong, Mizuta Kohei, Kang Byung Mo, Hozumi Chihiro, Bouvet Michael, Yamamoto Norio, Hayashi Katsuhiro, Kimura Hiroaki, Miwa Shinji, Igarashi Kentaro, Higuchi Takashi, Tsuchiya Hiroyuki, Demura Satoru, Hoffman Robert M
AntiCancer Inc., San Diego, CA, U.S.A.
Department of Surgery, University of California, San Diego, CA, U.S.A.
Anticancer Res. 2025 Feb;45(2):451-455. doi: 10.21873/anticanres.17434.
BACKGROUND/AIM: Ivermectin is a widely-used anti-parasitic agent and has shown early promise as an anticancer agent. Recombinant methioninase (rMETase) is a methionine-depleting enzyme targeting the methionine addiction of cancer and has broad efficacy against all tested cancer types. However, the combination efficacy of ivermectin and rMETase on breast cancer cells remains unexplored. The present study aimed to determine the synergistic efficacy of ivermectin and rMETase on MCF-7 human breast cancer cells in vitro.
The IC of ivermectin and IC of rMETase were determined on MCF-7 cells using the WST-8 reagent to measure cell viability in vitro. MCF-7 cells were treated with four groups: untreated control; ivermectin alone (4.89 μM, IC); rMETase alone (2.75 U/ml, IC); and a combination of ivermectin (4.89 μM) and rMETase (2.75 U/ml). Cell viability was assessed 72 hours after treatment with the WST-8 reagent.
Treatment with ivermectin (4.89 μM) did not significantly reduce the viability of MCF-7 cells. rMETase (2.75 U/ml) alone significantly reduced MCF-7 cell viability compared to the control group. The combination of ivermectin and rMETase resulted in a significantly greater reduction in cell viability than either agent alone, including a 9.9-fold greater efficacy than ivermectin alone, demonstrating synergistic efficacy (p<0.05).
The combination of ivermectin and rMETase had synergistic efficacy against MCF-7 breast cancer cells in vitro. The present findings suggest that the combination of ivermectin and rMETase is a promising strategy for breast cancer requiring further preclinical and clinical evaluation.
背景/目的：伊维菌素是一种广泛使用的抗寄生虫药物，并且已初步显示出作为抗癌药物的前景。重组蛋氨酸酶（rMETase）是一种使蛋氨酸耗竭的酶，可针对癌症的蛋氨酸成瘾现象，对所有测试的癌症类型均具有广泛疗效。然而，伊维菌素和rMETase对乳腺癌细胞的联合疗效仍未得到探索。本研究旨在确定伊维菌素和rMETase对MCF-7人乳腺癌细胞的体外协同疗效。
使用WST-8试剂测定伊维菌素的半数抑制浓度（IC）和rMETase的IC，以测量体外细胞活力。MCF-7细胞分为四组进行处理：未处理的对照组；单独使用伊维菌素（4.89 μM，IC）；单独使用rMETase（2.75 U/ml，IC）；以及伊维菌素（4.89 μM）和rMETase（2.75 U/ml）联合使用。用WST-8试剂在处理72小时后评估细胞活力。
用伊维菌素（4.89 μM）处理并未显著降低MCF-7细胞的活力。与对照组相比，单独使用rMETase（2.75 U/ml）显著降低了MCF-7细胞的活力。伊维菌素和rMETase联合使用导致细胞活力的降低显著大于单独使用任何一种药物，包括比单独使用伊维菌素的疗效高9.9倍，显示出协同疗效（p<0.05）。
伊维菌素和rMETase联合使用对MCF-7乳腺癌细胞具有体外协同疗效。本研究结果表明，伊维菌素和rMETase联合使用是一种有前景的乳腺癌治疗策略，需要进一步进行临床前和临床评估。
