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Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cells ex vivo and in an in vivo mouse model

  • Authors:
    • Sharmineh Mansoori
    • Kristin Blom
    • Claes Andersson
    • Mårten Fryknäs
    • Rolf Larsson
    • Peter Nygren
  • View Affiliations / Copyright

    Affiliations: Department of Medical Sciences, Akademiska Hospital (Uppsala University Hospital), 751 85 Uppsala, Sweden, Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
    Copyright: © Mansoori et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 9
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    Published online on: October 31, 2025
       https://doi.org/10.3892/or.2025.9014
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Abstract

Mebendazole (Mbz), a well‑known anthelminthic drug, has demonstrated anticancer properties in tumor models and patients, and is thus under consideration for repositioning into an anticancer drug. Mbz is directly cytotoxic in cell lines by various mechanisms and acts indirectly via immunomodulation. In the present study, the anticancer effects of Mbz, alone and in combination with cytotoxic drugs, were further characterized using primary cultures of patient tumor cells ex vivo and the murine colon cancer cell line, CT26, in vitro and in vivo. Patient‑derived tumor cells from acute myeloid leukemia (AML) and ovarian, colorectal and renal cancer were exposed to Mbz alone and, for solid tumors and the CT26 cell line, in combination with irinotecan, cisplatin or gemcitabine (patient cells only). Cytotoxicity was assessed using the fluorometric microculture cytotoxicity assay. In vivo, the antitumor effects of Mbz and irinotecan, alone and in combination, were evaluated in the BALB/c CT26 colon cancer mouse model by tumor growth measurements and flow cytometric analysis of tumor immune cell infiltration. In the patient cell samples, Mbz showed modest single‑agent cytotoxicity, with the AML samples being the most sensitive, and displayed enhanced effects when combined with cytotoxic drugs, particularly irinotecan. CT26 cells showed modest dose‑independent sensitivity to Mbz, which enhanced the effect of both cisplatin and irinotecan. In vivo, Mbz and irinotecan both inhibited tumor growth, but the combination did not significantly outperform Mbz alone. Flow cytometry of the resected mouse tumors indicated that Mbz promoted macrophage polarization from the M2 to M1 phenotype, suggesting that immune modulation may contribute to its anticancer effect. Mbz has features making it a candidate for repositioning into an anticancer drug and part of its effect may be mediated by macrophage modulation.
View Figures

Figure 1

Representative image of
May-Grünwald-Giemsa-stained isolated cells at 10× magnification
from a patient with colorectal cancer.

Figure 2

Schematic illustration of the ex
vivo SI AUC for drugs alone and when combined with 5 µM Mbz.
Calculation of the AUC ratios
(AUCCombo/AUCSingle) were used for the
assessment of drug interactions ex vivo. SI, survival index;
AUC, area under the curve; Mbz, mebendazole.

Figure 3

SI of ex vivo patient tumor
cells exposed to the indicated Mbz concentrations for 72 h in (A)
acute myeloid leukemia (n=24), (B) ovarian cancer (n=78), (C)
colorectal cancer (n=71) and (D) renal cell cancer (n=49). Data are
presented as mean ± SD. *P<0.05, ***P<0.001 compared with
acute myeloid leukemia. SI, survival index; Mbz, mebendazole.

Figure 4

Heatmap of the ex vivo
relative sensitivity of individual samples of patient tumor cells
to 5 µM mebendazole in combination with cisplatin, gemcitabine or
irinotecan, for each diagnosis indicated. Values <1 indicate
subadditivity (synergy) and values >1 indicate antagonism.

Figure 5

Distribution of the interaction
scores calculated by SynergyFinder in 4 samples of colorectal
cancer for Mbz combined with irinotecan or cisplatin, and for each
of the four interaction models indicated. Scores in the −10 to +10
range suggest additive interaction, >10 synergistic and <-10
antagonistic interaction. *P<0.05. Mbz, mebendazole; Bliss,
Bliss excess; HSA, Highest Single Agent; Loewe, Loewe additivity;
ZIP, Zero Interaction Potency.

Figure 6

Tumor volumes over time in (A) mice
exposed to LD Mbz or (B) HD Mbz and their combinations with
irinotecan as well as effect of this drug alone. Treatment was
started at day 0. The control group (saline) is only presented up
to day 13 since most of the animals in this group had been
euthanized beyond that day. Results are presented as mean ± SD.
*P<0.05. LD, low dose; HD, high dose; Mbz, mebendazole.

Figure 7

Kaplan-Meier survival curves for the
control and experimental group mice. LD, low dose; HD, high dose;
Mbz, mebendazole.

Figure 8

Box-and-whiskers plots presenting the
immune cell populations in control and experimental group mice
measured by flow cytometry. (A) Total macrophages, (B)
CD4+ T cells, (C) CD8+ T cells, (D) M1
macrophages, (E) M2 macrophages and (F) M1/M2 ratio. Boxes
encompass 50% of the observations, the horizontal line in box is
the mean from 9 tumors analyzed and the whiskers indicate the
observation ranges. The M1/M2 ratio data is presented by log10
scale. *P<0.05. LD, low dose; HD, high dose; Mbz,
mebendazole.
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Spandidos Publications style
Mansoori S, Blom K, Andersson C, Fryknäs M, Larsson R and Nygren P: Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cells <em>ex vivo</em> and in an <em>in vivo</em> mouse model. Oncol Rep 55: 9, 2026.
APA
Mansoori, S., Blom, K., Andersson, C., Fryknäs, M., Larsson, R., & Nygren, P. (2026). Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cells <em>ex vivo</em> and in an <em>in vivo</em> mouse model. Oncology Reports, 55, 9. https://doi.org/10.3892/or.2025.9014
MLA
Mansoori, S., Blom, K., Andersson, C., Fryknäs, M., Larsson, R., Nygren, P."Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cells <em>ex vivo</em> and in an <em>in vivo</em> mouse model". Oncology Reports 55.1 (2026): 9.
Chicago
Mansoori, S., Blom, K., Andersson, C., Fryknäs, M., Larsson, R., Nygren, P."Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cells <em>ex vivo</em> and in an <em>in vivo</em> mouse model". Oncology Reports 55, no. 1 (2026): 9. https://doi.org/10.3892/or.2025.9014
Copy and paste a formatted citation
x
Spandidos Publications style
Mansoori S, Blom K, Andersson C, Fryknäs M, Larsson R and Nygren P: Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cells <em>ex vivo</em> and in an <em>in vivo</em> mouse model. Oncol Rep 55: 9, 2026.
APA
Mansoori, S., Blom, K., Andersson, C., Fryknäs, M., Larsson, R., & Nygren, P. (2026). Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cells <em>ex vivo</em> and in an <em>in vivo</em> mouse model. Oncology Reports, 55, 9. https://doi.org/10.3892/or.2025.9014
MLA
Mansoori, S., Blom, K., Andersson, C., Fryknäs, M., Larsson, R., Nygren, P."Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cells <em>ex vivo</em> and in an <em>in vivo</em> mouse model". Oncology Reports 55.1 (2026): 9.
Chicago
Mansoori, S., Blom, K., Andersson, C., Fryknäs, M., Larsson, R., Nygren, P."Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cells <em>ex vivo</em> and in an <em>in vivo</em> mouse model". Oncology Reports 55, no. 1 (2026): 9. https://doi.org/10.3892/or.2025.9014
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