Ivermectin Combined With Recombinant Methioninase (rMETase) Synergistically Eradicates MiaPaCa-2 Pancreatic Cancer Cells.

IF 1.6 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2025-01-01 DOI:10.21873/anticanres.17396

Sei Morinaga, Qinghong Han, Kohei Mizuta, Byung Mo Kang, Michael Bouvet, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Hiroyuki Tsuchiya, Satoru Demura, Robert M Hoffman

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引用次数: 0

Abstract

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.

Materials and methods: 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.

Results: The IC₅₀ of ivermectin for MiaPaCa-2 cells was 5.9 μM. The IC₅₀ 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).

Conclusion: 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.

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伊维菌素联合重组蛋氨酸酶协同根除MiaPaCa-2胰腺癌细胞

背景/目的：伊维菌素最初被用作兽药，对多种寄生虫有疗效。胰腺癌是目前最难治性疾病之一。本研究的目的是证明重组蛋氨酸酶（rMETase）和伊维菌素联合在体外根除人胰腺癌细胞中的协同作用。材料和方法：将MiaPaCa-2人胰腺癌细胞培养于添加10%胎牛血清和1 IU/ml青霉素/链霉素的Dulbecco's modified Eagle's培养基（DMEM）中。用wst试剂检测rMETase单独使用和伊维菌素单独使用及其联合使用对MiaPaCa-2细胞存活率的影响。实验分为四组：对照组不加处理；伊维菌素;rMETase孤独;伊维菌素联合rMETase。结果：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。伊维菌素（5.9 μM）联合rMETase （2.93 U/ml）与单独使用伊维菌素相比，可显著降低MiaPaCa-2细胞的活力（分别降低80%和45%）。结论：伊维菌素与rMETase联合使用可有效根除MiaPaCa-2胰腺癌细胞。目前的结果表明，目前作为膳食补充剂口服给药的rMETase和口服伊维菌素联合治疗胰腺癌的未来临床潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.