Frederik A Stuebs, Anna K Dietl, Carla E Schulmeyer, Annika S Behrens, Anja Seibold, Lena Brueckner, Oliver Schleicher, Werner Adler, Carol Geppert, Arndt Hartman, Antje Knöll, Matthias W Beckmann, Paul Gass, Ralf Hilfrich, Grit Mehlhorn
{"title":"Prognostic Significance of the Detection of Human Papilloma Virus L1 Protein in Smears of Cervical Intraepithelial Neoplasia Grade 3 in Pregnant Women.","authors":"Frederik A Stuebs, Anna K Dietl, Carla E Schulmeyer, Annika S Behrens, Anja Seibold, Lena Brueckner, Oliver Schleicher, Werner Adler, Carol Geppert, Arndt Hartman, Antje Knöll, Matthias W Beckmann, Paul Gass, Ralf Hilfrich, Grit Mehlhorn","doi":"10.21873/anticanres.17455","DOIUrl":"https://doi.org/10.21873/anticanres.17455","url":null,"abstract":"<p><strong>Background/aim: </strong>Cervical intraepithelial neoplasia (CIN) III/high-grade squamous lesions (HSIL) remains a significant challenge during pregnancy. Current data on the course of disease are contradictory, with cases of progression to cervical cancer (CC) during pregnancy being observed. Evidence suggests that the expression of L1 capsid protein is associated with a favorable prognosis in non-pregnant women. The aim of this study was to evaluate L1 expression in pregnant women with CIN III/HSIL.</p><p><strong>Patients and methods: </strong>Between 2008 and 2021, the conventional PAP-smears from pregnant women were retrospectively analyzed for the expression of L1. Only women with histologically confirmed CIN III/HSIL during pregnancy were included.</p><p><strong>Results: </strong>A total of 161 women were included in this study; among them, 32 women (19.9%) had regressive disease postpartum. The majority of women (n=123, 76.4%) had persistent disease. In six cases, invasive CC was histologically proven postpartum (3.7%). In 113 women (70.2%) the PAP-Smears were L1- and 29.2% (n=48) of women were L1+. The rates of regression for L1+ were higher than for L1-, 25% vs. 17.7%, respectively. Rates for persistence were similar, at 75% and 78%, respectively. All cases of progression to CC were L1 negative during pregnancy.</p><p><strong>Conclusion: </strong>In pregnant women, the rates of regression were higher in L1+ CIN III/HSIL cases. All women who progressed to CC were L1-. Therefore, detecting L1 expression could serve as a valuable test to rule out progression to CC in pregnant women. This approach may provide reassurance to women, allowing them to continue their pregnancies with reduced fear and anxiety about CIN III/HSIL during pregnancy.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 2","pages":"677-683"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pterostilbene Suppressed Cell Viability, Induced Apoptosis and Autophagy of Cisplatin-resistant Gastric Cancer Cells.","authors":"Chien-Jung Huang, Po-Chuen Shieh, Jai-Sing Yang, Yi-Chia Li, Yu-Jen Chiu, DA-Tian Bau, Chih-Hsin Hung","doi":"10.21873/anticanres.17440","DOIUrl":"https://doi.org/10.21873/anticanres.17440","url":null,"abstract":"<p><strong>Background/aim: </strong>Gastric cancer (GC) is one of the most common cancers worldwide. Cisplatin is a key therapeutic agent for treating GC. Currently, the resistance of GC cells to cisplatin remains a major concern. Pterostilbene (PTS) is a natural phytochemical found in blueberry and grape. The anti-cisplatin-resistant GC effects and pharmacological mechanisms of PTS are unknown.</p><p><strong>Materials and methods: </strong>We investigated the anticancer activity of PTS in cisplatin-resistant GC cells and explored its pharmacological mechanisms of action via cell viability assay, cell confluence assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, acridine orange (AO) staining, monodansylcadaverine (MDC) staining, caspase-9/-3 activity assay, and RNA sequencing (RNA-Seq) analysis.</p><p><strong>Results: </strong>Our results showed that PTS inhibited cell viability and cell confluence of cisplatin-resistant GC cells using the CCK-8 assay and the IncuCyte S3 ZOOM System. The TUNEL assay showed that PTS promoted apoptosis in cisplatin-resistant GC cells. PTS induced apoptosis by increasing caspase-9 and caspase-3 activity. PTS promoted cell autophagy by increasing vacuole formation and acidic vesicular organelles using MDC and AO staining. We also observed an increase in the expression of LC3B in PTS-treated cisplatin-resistant GC cells. RNA-Seq analysis demonstrated that PTS induced apoptosis and autophagy in cisplatin-resistant GC cells by decreasing the expression of ATM/ATR, HIF-1, PI3K, RB1CC, TBK1, and mitochondria-related genes.</p><p><strong>Conclusion: </strong>Our results suggested that PTS is a promising phytochemical for GC therapy, particularly against cisplatin resistance.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 2","pages":"511-523"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acyclic Retinoid Inhibits the EGFR/AKT Signaling Pathway and Cancels Cisplatin-resistant Cell Characteristics.","authors":"Makito Motoyama, Ryota Shigefuku, Noriyoshi Tanaka, Mitsuaki Nishizawa, Keigo Oshio, Yoshitomo Suhara, Ichiro Yajima","doi":"10.21873/anticanres.17432","DOIUrl":"https://doi.org/10.21873/anticanres.17432","url":null,"abstract":"<p><strong>Background/aim: </strong>Lung cancer is among the most prevalent and lethal malignancies worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Overactivation of the EGFR/AKT signaling pathway contributes significantly to NSCLC progression and metastasis. Cisplatin, a widely used chemotherapeutic agent, faces limitations due to severe side effects and the emergence of resistant cancer cells. Acyclic retinoid (ACR), a synthetic derivative of vitamin A, has shown antitumor effects in hepatocellular carcinoma, but its efficacy against NSCLC and cisplatin-resistant cells remains unclear. This study aimed to investigate whether ACR could inhibit EGFR/AKT signaling and enhance therapeutic efficacy against NSCLC and cisplatin-resistant cells.</p><p><strong>Materials and methods: </strong>Human NSCLC A549 cells, cisplatin-resistant A549 (A549CR) cells, and normal lung epithelial BEAS-2B cells were treated with ACR, alone or in combination with cisplatin. Cell viability, apoptosis, and changes in expression/phosphorylation of EGFR, AKT, and cell cycle regulators were assessed using cell viability assay, immunostaining, and immunoblotting.</p><p><strong>Results: </strong>ACR selectively reduced viability of A549 cells with less toxicity to BEAS-2B cells and induced apoptosis via cleaved Caspase-3 activation. ACR inhibited EGFR/AKT signaling and up-regulated p27<sup>KIP1</sup> in A549 cells. The combination of ACR and cisplatin synergistically reduced cell viability and suppressed AKT phosphorylation. Notably, ACR also inhibited EGFR/AKT signaling in A549CR cells, restoring sensitivity to cisplatin and reversing EMT-like characteristics.</p><p><strong>Conclusion: </strong>ACR effectively inhibits EGFR/AKT signaling and enhances cisplatin sensitivity in NSCLC and cisplatin-resistant cells, suggesting its potential as a promising therapeutic strategy for lung cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 2","pages":"433-443"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohd Rehan, Ishfaq A Sheikh, Mohd Suhail, Shams Tabrez, Shazi Shakil
{"title":"Computational Exploration of a Diverse Flavonoid Library for Targeted Allosteric Inhibition of AKT1 in Cancer Therapy.","authors":"Mohd Rehan, Ishfaq A Sheikh, Mohd Suhail, Shams Tabrez, Shazi Shakil","doi":"10.21873/anticanres.17446","DOIUrl":"https://doi.org/10.21873/anticanres.17446","url":null,"abstract":"<p><strong>Background/aim: </strong>AKT serine/threonine kinase 1 (AKT1) is an established therapeutic target in cancer therapy due to its role in promoting cell survival and proliferation. This study aimed to identify potential allosteric inhibitors of AKT1 from a large flavonoid library using computational methods.</p><p><strong>Materials and methods: </strong>A computational screening of a comprehensive flavonoid library to identify novel allosteric inhibitors targeting the AKT1 allosteric site was performed. Molecular docking identified compounds with favorable binding interactions and the top 10 were selected for binding pose analysis. Molecular dynamics simulations for 200 ns were further employed to assess the stability of the highest-ranked compound.</p><p><strong>Results: </strong>The study proposed 10 flavonoids as potential allosteric AKT1 inhibitors. The docking analysis highlighted critical interactions between the 10 flavonoids and AKT1, with residues such as Trp-80, Ile-84, Tyr-272, Arg-273 and Asp-292 playing significant roles in binding stability. Trp-80 emerged as a pivotal residue, consistently forming the highest number of non-bonding contacts across most compounds, corresponding with prior studies that identified it as essential for allosteric inhibition. The highest-ranked flavonoid, CID 108790283, demonstrated the strongest binding affinity, with a binding energy of -10.64 kcal/mol, 56 non-bonding contacts, and a hydrogen bond. Molecular dynamics simulations further confirmed the stability of this flavonoid within the allosteric site, exhibiting minimal conformational fluctuation throughout the 200-ns simulation.</p><p><strong>Conclusion: </strong>This computational investigation identified 10 flavonoids with strong interaction profiles and stable binding within the allosteric site of AKT1, suggesting their potential as novel AKT1 inhibitors. These findings provide a basis for further experimental studies to validate their efficacy in cancer treatment.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 2","pages":"593-604"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anti-tumor Effects of Erlotinib <i>via</i> Thymidylate Synthase Down-regulation in Pancreatic Cancer Cells.","authors":"Satoshi Tabuchi, Tetsuro Tominaga, Tomoshi Tsuchiya, Ryoichiro Doi, Jyunichi Arai, Takashi Nonaka, Takuro Miyazaki, Tatsuo Inamine, Kazuhiro Tsukamoto, Keitaro Matsumoto","doi":"10.21873/anticanres.17439","DOIUrl":"https://doi.org/10.21873/anticanres.17439","url":null,"abstract":"<p><strong>Background/aim: </strong>In pancreatic cancer, gemcitabine and EGFR tyrosine kinase inhibitors (EGFR-TKIs) are common chemotherapy options. Reports have shown that EGFR-TKIs suppress the expression of thymidine synthase (TS), an important enzyme for DNA biosynthesis, and increase sensitivity to gemcitabine in lung cancer. However, no such reports have been made in pancreatic cancer.</p><p><strong>Materials and methods: </strong>Human pancreatic cancer cell lines MiaPaCa2, Panc1, and BxPc3 were used. TS mRNA and protein expression levels in the cells were analyzed after erlotinib treatment. In addition, the anti-tumor effect of TS knockdown was verified using TS siRNA, along with its synergistic effect when combined with gemcitabine.</p><p><strong>Results: </strong>TS expression was high in MiaPaCa2 and Panc1 cells and low in BxPc3 cells. After erlotinib treatment, TS mRNA and protein levels decreased markedly in MiaPaCa2 cells dose-dependently, but not in Panc1 cells. TS siRNA caused specific down-regulation of TS in MiaPaCa2 and Panc1 cells. TS down-regulation resulted in an anti-tumor effect in these cells (MiaPaCa2 42%; Panc1 38%; p<0.05), showing a synergistic effect when combined with gemcitabine.</p><p><strong>Conclusion: </strong>Erlotinib could have a synergistic anti-tumor effect when combined with gemcitabine via down-regulation of TS expression.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 2","pages":"503-510"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterization of Patient-derived Xenograft Models of Liver Fluke-associated Cholangiocarcinoma: From Establishment to Molecular Profiling.","authors":"Hasaya Dokduang, Apiwat Jarernrat, Attapol Titapun, Sirinya Sitthirak, Sureerat Padthaisong, Yingpinyapt Kittirat, Sakkarn Sangkamanon, Prakasit Sa-Ngiamwibool, Arporn Wangwiwatsin, Poramate Klanrit, Nisana Namwat, Apinya Jusakul, Yoshinori Murakami, Watcharin Loilome","doi":"10.21873/anticanres.17445","DOIUrl":"https://doi.org/10.21873/anticanres.17445","url":null,"abstract":"<p><strong>Background/aim: </strong>Cholangiocarcinoma (CCA) is an aggressive cancer with limited effective chemotherapy and targeted therapy options. Existing cell lines and animal models only partially mimic the characteristics of the tumor, highlighting the need for more effective models to study the biology of cancer and drug responses. This study aimed to establish and characterize patient-derived xenograft (PDX) models of CCA.</p><p><strong>Materials and methods: </strong>Tumor samples from 40 CCA patients were subcutaneously implanted into non-obese diabetic/ShiJic-severe combined immunodeficiency Jcl mice to establish patient-derived xenograft (PDX) models. Successfully engrafted tumors were passaged across three generations. Histological features were analyzed using H&E staining and immunohistochemistry for cytokeratin-19, cytokeratin-7, heppar-1 and arginase-1. Whole exome sequencing (WES) was performed to assess genetic stability and identify somatic mutations.</p><p><strong>Results: </strong>A total of eight PDX models were successfully created, representing 20% of the total cases. Histological comparisons showed strong concordance between patient tumors and their corresponding xenografts in the eight PDX models across generations. WES analysis confirmed the genetic stability of the PDX models, with significant somatic mutations identified in key genes such as TTN, MUC12, ARID1A, TP53, and RNF43.</p><p><strong>Conclusion: </strong>The CCA PDX model could reflect both the histological and genetic characteristics of the original tumors, providing a valuable tool for studying tumor biology and serving as a preclinical model to develop personalized treatment options for CCA.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 2","pages":"579-592"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dirk Rades, Charlotte Kristiansen, Christine Vestergaard Madsen, Jan-Dirk Küter, Laura Splettstösser, Cathrin Thieme, Jon Cacicedo, Stefan Janssen
{"title":"Bladder Volume <200 ml During a Course of Moderate Hypofractionated Irradiation in Patients With Localized Prostate Cancer.","authors":"Dirk Rades, Charlotte Kristiansen, Christine Vestergaard Madsen, Jan-Dirk Küter, Laura Splettstösser, Cathrin Thieme, Jon Cacicedo, Stefan Janssen","doi":"10.21873/anticanres.17458","DOIUrl":"10.21873/anticanres.17458","url":null,"abstract":"<p><strong>Background/aim: </strong>Hypo-fractionated radiotherapy (HF-RT) is gaining popularity in prostate cancer treatment. HF-RT can lead to cystitis, particularly in cases with small bladder volumes. This study evaluated the bladder volume during a course of moderate HF-RT. This knowledge is required for the protocol of a prospective trial.</p><p><strong>Patients and methods: </strong>Seventy-six patients receiving HF-RT (20×3.0 Gy) for prostate cancer were retrospectively evaluated. The number of HF-RT sessions with a bladder volume <200 ml and corresponding risk factors were investigated.</p><p><strong>Results: </strong>Mean and median numbers of sessions with a bladder volume <200 ml were 13.4 (±6.7) and 16.0 (interquartile range=8.0-19.0), respectively. Higher numbers of radiotherapy sessions with a bladder volume <200 ml were associated with a pre-radiotherapy volume <200 ml (p<0.001). Mean numbers of sessions with a bladder volume <200 ml were 16.0 (±5.5) in patients with a pre-radiotherapy bladder volume <200 ml and 7.9 (±5.9) in patients with a bladder volume ≥200 ml, respectively.</p><p><strong>Conclusion: </strong>Bladder volume was <200 ml during many HF-RT sessions. Patients with a pre-radiotherapy bladder volume <200 ml may benefit from an app reminding them to drink water before their HF-RT sessions.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 2","pages":"701-708"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association of <i>Matrix Metalloproteinase-1</i> Promoter Genotypes With Endometriosis Risk.","authors":"Po-Chuen Shieh, Hou-Yu Shih, Chin-Liang Chuang, Chia-Wen Tsai, Wen-Shin Chang, Meng-Gi Bau, Yun-Chi Wang, Te-Chun Hsia, DA-Tian Bau, Jai-Sing Yang","doi":"10.21873/anticanres.17436","DOIUrl":"https://doi.org/10.21873/anticanres.17436","url":null,"abstract":"<p><strong>Background/aim: </strong>Over-expression of matrix metalloproteinase-1 (MMP-1) has been suggested as a biomarker for endometriosis. However, the genetic influence of MMP-1 in the pathogenesis of endometriosis remains unclear, with its role yet to be fully elucidated. This study aimed to investigate the association between MMP-1 rs1799750 promoter polymorphisms and the risk of developing endometriosis.</p><p><strong>Patients and methods: </strong>This hospital-based case-control study included 203 women diagnosed with endometriosis and 636 age-matched controls. Genotyping of the MMP-1 rs1799750 polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.</p><p><strong>Results: </strong>Among the patients with endometriosis, the distribution of genotypes 2G/2G, 2G/1G, and 1G/1G at MMP-1 rs1799750 was 52.7%, 41.4%, and 5.9%, respectively. This distribution significantly differed from that of the control group, which exhibited frequencies of 41.3%, 48.3%, and 10.4%, respectively (p for trend=0.0092). In the dominant model, carriers of the 2G/1G and 1G/1G genotypes had a reduced prevalence in the endometriosis group compared to 2G/2G carriers [odds ratio (OR)=0.63, 95% confidence interval (95%CI)=0.46-0.87, p=0.0058]. Additionally, the 1G allele frequency in the endometriosis group was 26.6%, significantly lower than the 34.5% observed in controls (OR=0.69, 95%CI=0.54-0.88, p=0.0037).</p><p><strong>Conclusion: </strong>The 1G allele of MMP-1 rs1799750 is associated with reduced susceptibility to endometriosis in the Taiwanese population. These results highlight the potential of MMP-1 rs1799750 polymorphism as a protective genetic marker, warranting further investigations to explore its genotype-phenotype correlation and underlying biological mechanisms.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 2","pages":"465-471"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sei Morinaga, Qinghong Han, Kohei Mizuta, Byung Mo Kang, Chihiro Hozumi, Michael Bouvet, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Hiroyuki Tsuchiya, Satoru Demura, Robert M Hoffman
{"title":"Recombinant Methioninase (rMETase) Synergistically Sensitizes Ivermectin-resistant MCF-7 Breast Cancer Cells 9.9 Fold to Low-dose Ivermectin.","authors":"Sei Morinaga, Qinghong Han, Kohei Mizuta, Byung Mo Kang, Chihiro Hozumi, Michael Bouvet, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Hiroyuki Tsuchiya, Satoru Demura, Robert M Hoffman","doi":"10.21873/anticanres.17434","DOIUrl":"https://doi.org/10.21873/anticanres.17434","url":null,"abstract":"<p><strong>Background/aim: </strong>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.</p><p><strong>Materials and methods: </strong>The IC<sub>10</sub> of ivermectin and IC<sub>50</sub> 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<sub>10</sub>); rMETase alone (2.75 U/ml, IC<sub>50</sub>); 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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 2","pages":"451-455"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}