Abstract
Introduction. Introduction. Prostate cancer (PCa) is a leading cause of cancer-related mortality among men worldwide. Current treatments, including docetaxel chemotherapy, often have limited efficacy and are associated with side effects. Berberine, a natural compound with established antitumor properties, has been shown to enhance the effects of chemotherapeutic agents.
Aim. To investigate the combined effect of berberine and docetaxel on the viability and proliferation of PCa cell lines PC-3, LNCaP, and DU-145 in vitro, and to assess the nature of their interaction (synergism, additivity, or antagonism).
Materials and Methods. The study was conducted on PCa cell cultures. Cells were treated with various concentrations of berberine and docetaxel, both alone and in combination. Cell viability was assessed using the MTT assay after 24 and 72 hours of incubation. Drug interactions were analyzed using a linear interaction effect model, and coefficients of synergism, additivity, or antagonism were calculated. Statistical significance was determined by ANOVA and Tukey's test.
Results. The PC-3 cell line showed the highest sensitivity to berberine. The combination of berberine and docetaxel did not demonstrate a synergistic effect; interaction coefficients exceeded 1, indicating additive or antagonistic interactions, particularly at low berberine concentrations. No sensitization of cells to docetaxel was observed following pre-treatment with berberine. Mathematical analysis of the results indicated antagonism between the two compounds.
Conclusion. Berberine exhibits an antagonistic effect when combined with docetaxel in PC-3, LNCaP, and DU-145 PCa cell cultures.
References
Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019; 10(2): 63-89.-DOI: https://doi.org/10.14740/wjon1191.
International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today. Data visualization tools for exploring the global cancer burden in 2022. 1965-2026. Lyon, France: IARC; -URL: https://gco.iarc.fr/today/en.
Каприн А.Д., Старинский В.В., Шахзадова А.О. Состояние онкологической помощи населению России в 2021 году. М.: МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России. 2022; 28. [Kaprin A.D., Starinsky V.V., Shakhzadova A.O. The state of cancer care in Russia in 2021. Moscow: P.A. Herzen Moscow State Medical Research Institute — branch of the Federal State Budgetary Institution ‘NMRC of Radiology’ of the Ministry of Health of Russia. 2022; 28 (In Rus)].
Berlin I.G., Jennings C.C., Shin S., Kenealey J. Utilizing mixture design response surface methodology to determine effective combinations of plant derived compounds as prostate cancer treatments. Cancer Rep (Hoboken). 2023; 6(4): e1790.-DOI: https://doi.org/10.1002/cnr2.1790.
Sajeev A., Sailo B., Unnikrishnan J., et al. Unlocking the potential of Berberine: Advancing cancer therapy through chemosensitization and combination treatments. Cancer Lett. 2024; 597: 217019.-DOI: https://doi.org/10.1016/j.canlet.2024.217019.
Duarte D., Vale N. Evaluation of synergism in drug combinations and reference models for future orientations in oncology. Curr Res Pharmacol Drug Discov. 2022; 12; 3: 100110.-DOI: https://doi.org/10.1016/j.crphar.2022.100110.
Fizazi K., Foulon S., Carles J., et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022; 399(10336): 1695-1707.-DOI: https://doi.org/10.1016/S0140-6736(22)00367-1.
Aziz M.K., Molony D., Monlezun D., et al. Prostate cancer therapy cardiotoxicity map (PROXMAP) for advanced disease states: a systematic review and network meta-analysis with Bayesian modeling of treatment histories. Eur Urol. 2025; 87(1): 15-26.-DOI: https://doi.org/10.1016/j.eururo.2024.08.031.
Newman D.J., Cragg G.M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod. 2020; 83(3): 770-803.-DOI: https://doi.org/10.1021/acs.jnatprod.9b01285.
Златник Е.Ю., Енин Я.С., Буров О.Н., et al. Молекулярно-клеточные аспекты воздействия вторичных метаболитов Барбариса обыкновенного и Белокопытника гибридного на клеточную линию HeLa. Исследования и практика в медицине. 2023; 10(4): 31-47.-DOI: https://doi.org/10.17709/2410-1893-2023-10-4-3. [Zlatnik E.Yu., Enin Ya.S., Burov O.N., et al. Molecular and cellular aspects of the effect of secondary metabolites of common barberry and hybrid butterbur on the HeLa cell line. Research and Practice in Medicine. 2023; 10(4): 31-47.-DOI: https://doi.org/10.17709/2410-1893-2023-10-4-3 (In Rus)].
Тимофеева С.В., Златник Е.Ю., Ващенко Л.Н., et al. Молекулярные механизмы влияния берберина на опухолевые клетки. Казанский медицинский журнал. 2025; 106(2): 267-276.-DOI: https://doi.org/10.17816/KMJ643366. [Timofeeva S.V., Zlatnik E.Yu., Vashchenko L.N., et al. Molecular mechanisms of berberine effect on tumor cells. Kazan Medical Journal. 2025; 106(2): 267-276.-DOI: https://doi.org/10.17816/KMJ643366 (In Rus)].
Mezhevova I.V., Filippova S.Yu., Timofeeva S.V., et al. Antimigratory effect of berberine in T98G, U87MG and primary glioma cell culture. J Clin Oncol. 2021; 39(S15): e15045.-DOI: https://doi.org/10.1200/JCO.2021.39.15_suppl.e15045.
Zheng S., Wang W., Aldahdooh J., et al. SynergyFinder plus: Toward better interpretation and annotation of drug combination screening datasets. Genomics, J Proteom Bioinform. 2022; 20: 587-596.-DOI: https://doi.org/10.1016/j.gpb.2022.01.004.
Bao J., Huang B., Zou L., et al. Hormetic effect of berberine attenuates the anticancer activity of chemotherapeutic agents. PLoS One. 2015; 10(9): e0139298.-DOI: https://doi.org/10.1371/journal.pone.0139298.
Zou P., Li S., He Q., Zheng C. Berberine inhibits prostate cancer progression by inducing ferroptosis: evidence from network pharmacology. Anticancer Drugs. 2025; 36(4): 271-279.-DOI: https://doi.org/10.1097/CAD.0000000000001691.
Lu X., Yang F., Chen D., et al. Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways. Int J Biol Sci. 2020; 16(7): 1121-1134.-DOI: https://doi.org/10.7150/ijbs.41686.
Campos-Fernandez E., Alqualo N.O., Garcia L.C.M., et al. The use of aptamers in prostate cancer: A systematic review of theranostic applications. Clin Biochem. 2021; 93: 9-25-DOI: https://doi.org/10.1016/j.clinbiochem.2021.03.014.
Sienkiewicz K., Yang C., Paschal B.M., Ratan A. Genomic analyses of the metastasis-derived LNCaP, VCaP, and PC3-AR. Prostate Cancer Cell Lines. 2021: 449904.-DOI: https://doi.org/10.1101/2021.06.25.449904.
Tian Y., Zhao L., Wang Y., et al. Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells. Asian J Androl. 2016; 18(4): 607-12.-DOI: https://doi.org/10.4103/1008-682X.169997.
Тимофеева С.В., Филиппова С.Ю., Ситковская А.О., et al. Биоресурсная коллекция клеточных линий и первичных опухолей ФГБУ НМИЦ онкологии Минздрава России. Кардиоваскулярная терапия и профилактика. 2022; 21(11): 3397.-DOI: https://doi.org/10.15829/1728-8800-2022-3397. [Timofeeva S.V., Filippova S.Yu., Sitkovskaya A.O., et al. Bioresource collection of cell lines and primary tumors of the Federal State Budgetary Institution National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. Cardiovascular Therapy and Prevention. https://doi.org/10.15829/1728-8800-2022-3397 (In Rus)].
Филиппова С.Ю., Ситковская А.О., Тимофеева С.В., et al. Применение силиконового покрытия для оптимизации процесса получения клеточных сфероидов методом висячей капли. Южно-Российский онкологический журнал/ South Russian Journal of Cancer. 2022; 3(3): 15-23.-DOI: https://doi.org/10.37748/2686-9039-2022-3-3-2. [Filippova S.Yu., Sitkovskaya A.O., Timofeeva S.V., et al. Application of silicone coating to optimize the process of obtaining cell spheroids by the hanging drop method. South-Russian Journal of Oncology. 2022; 3(3): 15-23.-DOI: https://doi.org/10.37748/2686-9039-2022-3-3-2 (In Rus)].
Zhou S., Zeng S., Shu Y. Drug-drug interactions at organic cation transporter 1. Front Pharmacol. 2021; 12: 628705.-DOI: https://doi.org/10.3389/fphar.2021.628705.

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