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Inhibition of growth of colorectal cancer patient-derived subcutaneous xenografts using combined Wnt signaling pathway inhibitor and 5‑fluorouracil
Author(s) -
А. С. Гончарова,
A. V. Volkova,
Д. В. Ходакова,
G. Yu. Egorov,
A. Yu. Maksimov,
Evgeniy N. Kolesnikov,
Е. Ф. Комарова,
A. A. Kiblitskaya,
E. V. Zaikina,
L. Z. Kurbanova,
M. V. Mindar
Publication year - 2022
Publication title -
issledovaniâ i praktika v medicine
Language(s) - English
Resource type - Journals
eISSN - 2410-1893
pISSN - 2409-2231
DOI - 10.17709/2410-1893-2022-9-1-3
Subject(s) - fluorouracil , colorectal cancer , medicine , wnt signaling pathway , combination therapy , pharmacology , chemotherapy , cancer , oncology , cancer research , signal transduction , biology , biochemistry
Purpose of the study. Was to analyze antitumor efficacy of the XAV 939 Wnt signaling pathway inhibitor and its combination with 5 fluorouracil in subcutaneous xenografts derived from patients with colorectal cancer. Materials and methods . Antitumor efficacy of the agents and their combination was studied in xenografts derived from patients with colorectal cancer and subcutaneously implanted in immunodeficient Balb/c Nude mice. All animals with tumors were divided into 4 groups (n = 5): group 1 received 5 fluorouracil 25 mg/kg, group 2 – XAV 939 25 mg/kg, group 3–5 fluorouracil and XAV 939 combination at the same dosages, group 4 was control. Criteria for the efficacy of the tested agents and their combination included tumor growth rate and tumor growth inhibition rate (TGI %). Results . The mean volumes of xenografts and tumor growth rate in the group receiving a combination of 5 fluorouracil and XAV 939 were 335.2 ± 40.7 mm3 , being lower than the averages of xenografts in controls – 609.3 ± 69.5 mm3 (p < 0.05). The mean volumes of xenografts in the group receiving 5 fluorouracil monotherapy were 601.9 ± 45.5 mm3 , in the group with the XAV 939 monotherapy – 527.9 ± 258.6 mm3 . The highest TGI (44.99 %) was registered in the group receiving a combination of 5 fluorouracil and XAV 939. Conclusion . The study revealed the ability of combined XAV 939 Wnt signaling pathway inhibitor and 5 fluorouracil to inhibit the growth of subcutaneous xenografts derived from patients with colorectal cancer.

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