Cytostatic effect of ricobendazole on primary cultures of soft tissue sarcomas in vitro
S. Yu. Filippova,
T. V. Ausheva,
I. V. Mezhevova,
T. V. Chembarova,
N. V. Gnennaya,
I. A. Novikova,
A. Yu. Maksimov,
S. S. Alihanova,
K. S. Eremin,
A. S. Vatulina,
A. V. Snezhko,
M. A. Konovalchik https://doi.org/10.37748/2686-9039-2025-6-4-3
EDN: EZOHHX
Abstract
Soft tissue sarcomas (STS) are often resistant to treatment. The search for new antitumor compounds against STS remains an urgent task.
Purpose of the study. To assess the sensitivity of primary STS cultures of various histological subtypes to albendazole sulfoxide (ricobendazole) and doxorubicin, the primary metabolite of albendazole.
Materials and methods. STS tumor samples were used. The enzymatic dissociation method was used using 300 units/ml collagenase I (Thermo Fisher Scientific, USA). Ricasol® (NITA-PHARM, Russia) and Doxorubicin-LENS® (VEROPHARM, Russia) were used as test substances. Sensitivity to ricobendazole and doxorubicin was tested using the MTT test. The cultures were seeded in a 96‑well plate at 7,000 cells in DMEM medium with 10 % FSC added. After 24 h, the medium was replaced with PPS with ricobendazole in a series of two-fold dilutions from 35.5 μmol/l to 0.0347 μmol/l or doxorubicin from 10 μmol/l to 0.009 μmol/l. After 72 hours of incubation, the MTT test was performed. The cells were seeded in a 24‑well plate and cultured in PPS with 2 μmol/l ricabendazole for 72 h. Hoechst 33342 dye (Life Technologies, USA) was added to the culture at a concentration of 1 μg/ml, and photographs were taken using a LionHeart FX digital automatic microscope (BioTek Instruments Inc., USA).
Results. Four primary sarcoma cultures were obtained: SAR‑1, SAR‑2, SAR‑3, and SAR‑4. SAR-1 and SAR-4. Cultures demonstrated the most rapid growth, with doubling times of 38 and 27 hours, respectively. The slowest proliferation was observed in the SAR-2 culture (doubling time 156 hours), while SAR-3 showed a doubling time of 45 hours. According to the MTT assay, the IC50 values for ricobendazole were 4.54 ± 1.2 μmol/L for SAR-1, 3.31 ± 0.7 μmol/L for SAR-3, and 1.51 ± 0.2 μmol/L for SAR-4, whereas the slowly dividing SAR-2 culture proved to be insensitive to ricobendazole. The cytostatic activity of doxorubicin was higher than that of ricobendazole. The SAR‑2 culture was the least sensitive (IC50 could not be determined), and SAR‑4 (IC50 SAR‑4 = 0.16 ± 0.01 μmol/l) was the most sensitive to the action of doxorubicin. The IC50 value of SAR‑1 = 0.64 ± 0.02 μmol/l and IC50 SAR‑3 = 1.8 ± 0.1 μmol/l. The effect of ricobendazole caused pronounced disturbances in the nuclei of SAR‑1 and SAR‑4 cultures, in SAR‑2 and SAR‑3 they were less pronounced.
Conclusion. Ricobenzale had a cytostatic effect on primary STS cultures characterized by rapid cell growth, but the activity was lower than that of doxorubicin. Changes in the morphology of cells and nuclei indicated probable disturbances in the functioning of the spindle and cytoskeleton occurring under the action of this compound. Of particular interest for further research is the combination of ricobendazole with taxanes and other tubulin inhibitors.
About the Authors
S. Yu. Filippova
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Svetlana Yu. Filippova – Researcher, Laboratory of Cell Technologies, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-4558-5896, eLibrary SPIN: 9586-2785, AuthorID: 878784, Scopus Author ID: 57189618843, WoS ResearcherID: AAH-4408-2020
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
T. V. Ausheva
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Tatiana V. Ausheva – Cand. Sci. (Med.), MD, oncologist at the Department of Tumors of Bones, Skin, Soft Tissues and Breast, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-7073-9463, eLibrary SPIN: 5069-4010, AuthorID: 264138, Scopus Author ID: 57221315287, WoS ResearcherID: AAQ-9943-2020
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
I. V. Mezhevova
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Irina V. Mezhevova – Junior Researcher, Laboratory of Cell Technologies, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-7902-7278, eLibrary SPIN: 3367-1741, AuthorID: 1011695, Scopus Author ID: 57296602900, WoS ResearcherID: AAI-1860-2019
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
T. V. Chembarova
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Tatiana V. Chembarova – Junior Researcher, Laboratory of Cell Technologies, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-4555-8556, eLibrary SPIN: 5426-1873, AuthorID: 1051985, Scopus Author ID: 57221303597, WoS ResearcherID: AAR-3198-2021
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
N. V. Gnennaya
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Nadezhda V. Gnennaya – Junior Researcher, Laboratory of Cell Technologies, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-3691-3317, eLibrary SPIN: 9244-2318, AuthorID: 900758, Scopus Author ID: 57214806863, WoS ResearcherID: AGO-3908-2022
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
I. A. Novikova
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Inna A. Novikova – Dr. Sci. (Med.), Associate Professor, Deputy General Director for Science, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-6496-9641, eLibrary SPIN: 4810-2424, AuthorID: 726229, Scopus Author ID: 57202252773, WoS ResearcherID: E-7710-2018
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
A. Yu. Maksimov
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Aleksey Yu. Maksimov – Dr. Sci. (Med.), Professor, Deputy CEO for Advanced Scientific Research, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-9471-3903, eLibrary SPIN: 7322-5589, AuthorID: 710705, Scopus Author ID: 56579049500
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
S. S. Alihanova
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Sarizhat S. Alihanova – PhD student, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0009-0006-6454-2564, WoS ResearcherID: MIT-6736-2025
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
K. S. Eremin
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Konstantin S. Eremin – MD, pathologist, Department of Pathology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0001-9331-3353, eLibrary SPIN: 9865-0123, AuthorID: 1150930, WoS ResearcherID: AIE-7050-2022
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
A. S. Vatulina
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Anastasia S. Vatulina – MD, clinical laboratory diagnostics physician, laboratory geneticist, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0003-0685-9628, WoS ResearcherID: MIT-2080-2025
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
A. V. Snezhko
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Aleksandr V. Snezhko – Dr. Sci. (Medicine), Associate Professor of the Department of Oncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0003-3998-8004, eLibrary SPIN: 2913-3744, AuthorID: 439135
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
M. A. Konovalchik
https://www.rnioi.ru
National Medical Research Centre for Oncology
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Mariya A. Konovalchik – Cand. Sci. (Biology), Senior Researcher of Tumor Immunophenotyping Laboratory, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-9962-7318, eLibrary SPIN: 9724-0766, AuthorID: 881434, Scopus Author ID: 57198801957, WoS ResearcherID: JDM-5543-2023
Competing Interests:
The author Aleksey Yu. Maksimov serves as Deputy Editor-in-Chief of the South Russian Journal of Cancer. The author Aleksandr V. Snezhko is a member of the Editorial Board of the South Russian Journal of Cancer. The article underwent the standard peer-review procedure accepted by the Journal and was evaluated by independent experts. The authors did not declare any other conflicts of interest.
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For citations:
Filippova S.Yu., Ausheva T.V., Mezhevova I.V., Chembarova T.V., Gnennaya N.V., Novikova I.A., Maksimov A.Yu., Alihanova S.S., Eremin K.S., Vatulina A.S., Snezhko A.V., Konovalchik M.A. Cytostatic effect of ricobendazole on primary cultures of soft tissue sarcomas in vitro. South Russian Journal of Cancer. 2025;6(4):26-35. https://doi.org/10.37748/2686-9039-2025-6-4-3. EDN: EZOHHX
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