Morinaga Sei, Han Qinghong, Mizuta Kohei, Kang Byung Mo, 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 Jan;45(1):97-103. doi: 10.21873/anticanres.17396.
BACKGROUND/AIM: Ivermectin was initially utilized as a veterinary medication, demonstrating efficacy against various parasites. Pancreatic cancer is currently one of the most recalcitrant diseases. The aim of the present study was to demonstrate the synergy of the combination of recombinant methioninase (rMETase) and ivermectin to eradicate human pancreatic cancer cells in vitro.
MiaPaCa-2 human pancreatic cancer cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with the addition of 10% fetal bovine serum and 1 IU/ml penicillin/streptomycin. Reduction of cell viability by rMETase alone and ivermectin alone and their combination on MiaPaCa-2 cells was determined with the WST-reagent. Four experimental groups were examined in vitro: control group without treatment; ivermectin alone; rMETase alone; ivermectin combined with rMETase.
The IC of ivermectin for MiaPaCa-2 cells was 5.9 μM. The IC of rMETase on MiaPaCa-2 cells was 2.93 U/ml. Ivermectin (5.9 μM) plus rMETase (2.93 U/ml) synergistically greatly reduced the viability of MiaPaCa-2 cells, compared to ivermectin alone (80% reduction vs. 45% reduction, respectively p<0.05).
The combination of ivermectin and rMETase effectively eradicated MiaPaCa-2 pancreatic cancer cells. The present results indicate the future clinical potential of the combination of rMETase, currently administered orally to patients as a dietary supplement, and oral ivermectin on pancreatic cancer.
背景/目的：伊维菌素最初用作兽药，对多种寄生虫显示出疗效。胰腺癌是目前最难治疗的疾病之一。本研究的目的是证明重组蛋氨酸酶（rMETase）和伊维菌素联合使用在体外根除人胰腺癌细胞的协同作用。
将MiaPaCa-2人胰腺癌细胞培养在添加了10%胎牛血清和1 IU/ml青霉素/链霉素的杜氏改良 Eagle 培养基（DMEM）中。用WST试剂测定单独使用rMETase、单独使用伊维菌素及其组合对MiaPaCa-2细胞活力的降低情况。在体外检查了四个实验组：未处理的对照组；单独使用伊维菌素；单独使用rMETase；伊维菌素与rMETase联合使用。
伊维菌素对MiaPaCa-2细胞的IC50为5.9 μM。rMETase对MiaPaCa-2细胞的IC50为2.93 U/ml。与单独使用伊维菌素相比，伊维菌素（5.9 μM）加rMETase（2.93 U/ml）协同显著降低了MiaPaCa-2细胞的活力（分别为80%降低对45%降低，p<0.05）。
伊维菌素和rMETase联合使用有效根除了MiaPaCa-2胰腺癌细胞。目前作为膳食补充剂口服给患者的rMETase与口服伊维菌素联合使用对胰腺癌的结果表明了其未来的临床潜力。
