The role of 5-fluorouracil in Wnt/β-catenin signalling in human papillomavirus-positive cervical cancer cells.
Función del 5-fluorouracilo en la señalización Wnt/β-catenina en células de cáncer de cuello uterino positivas al virus del papiloma humano.
Abstract
Human papillomavirus (HPV) infection is a major risk factor for cervical cancer, especially persistent infection with high-risk HPV. 5-fluorouracil (5-FU) is a widely used antimetabolite chemotherapeutic agent that inhibits the proliferation of tumour cells by interfering with ribonucleic acid and deoxyribonucleic acid synthesis; however, its mechanism of action has not been fully elucidated. This study aimed to investigate the role of Wnt/ β-catenin signalling in patients with high-risk HPV with cervical cancer treated with 5-FU. Patients with high-risk HPV-positive cervical cancer treated with surgery were taken as the research participants, and lesion tissues were collected during surgery. Human HPV-positive cervical cancer cells were isolated and cultured in vitro by the enzyme combined digestion method, and the obtained cells were divided into a control group, a paclitaxel group and a 5-FU group. A 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to measure the proliferation of high-risk HPV-positive cervical cancer cells under different treatment conditions. Western blotting was used to evaluate the protein expression level of the Wnt/β-catenin signalling pathway in cells, and flow cytometry was used to analyse the level of T lymphocytes in the patients’ blood. The results of the MTT assay showed that the proliferation rate of cervical cancer cells in the control group was significantly higher than that in the paclitaxel group and the 5-FU group at all detection time points (p<0.05). The expression levels of Wnt/β- catenin protein in the 5-FU group were lower than those in the paclitaxel and the control groups (p<0.05). The results of the T lymphocyte level comparison showed that the ratios of CD3+ T cells, CD4+ T cells and CD4+ /CD8+ cells affected by 5-FU were higher than those before treatment (p<0.05). 5-fluorouracil can significantly reduce the expression level of Wnt/β-catenin protein and increase the T lymphocyte levels in cervical cancer cells.
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References
Cai X, Xu L. Human papillomavirus-related cancer vaccine strategies. Vaccines (Basel). 2024;12(11):1291. doi: 10.3390/vaccines12111291.
Shoaib S, Islam N, Yusuf N. Phytocompounds from the medicinal and dietary plants: Multi-target agents for cervical cancer prevention and therapy. Curr Med Chem. 2022;29(26):4481-4506. doi: 10.2174/0929867329666220301114251
Sindhuja T, Bhari N, Gupta S. Asian guidelines for condyloma acuminatum. J Infect Chemother. 2022;28(7):845-852. doi: 10.1016/j.jiac.2022.03.004.
Zheng S, Zhang X, Pang Z, Liu J, Liu S, Sheng R. Anti-Pan-Rspo Chimeric Protein-Conjugated Albumin Nanoparticle provides promising opportunities in cancer targeted therapy. Adv Health Mater. 2023;12(29):e2301441. doi: 10.1002/ad hm.202301441.
Pourhanifeh MH, Darvish M, Tabatabaeian J, Fard MR, Mottaghi R, Azadchehr MJ, Jahanshahi M, Sahebkar A, Mirzaei H. Therapeutic role of curcumin and its novel formulations in gynecological cancers. J Ovarian Res. 2020;13(1):130. doi: 10.1186/s13048-020-00731-7.
Shigeishi H. Association between human papillomavirus and oral cancer: a literature review. Int J Clin Oncol. 2023;28(8):982989. doi: 10.1007/s10147-023-02327-9.
Trujano-Camacho S, Cantú-de León D, Pérez-Yepez E, Contreras-Romero C, Coronel-Hernandez J, Millan-Catalan O, Rodríguez-Dorantes M, López-Camarillo C, Gutiérrez-Ruiz C, Jacobo-Herrera N, Pérez-Plasencia C. HOTAIR promotes the hyperactivation of PI3K/Akt and Wnt/β- Catenin signaling pathways via PTEN hypermethylation in cervical cancer. Cells. 2024;13(17):1484. doi: 10.3390/cells13171484.
Kamate B, Kassogue Y, Diakite B, Traore B, Cisse K, Diarra F, Kassogue O, Diarra M, Coulibaly A, Coulibaly B, Maiga A, Ly M, Diallo H, Sissoko SB, Sissoko AS, Traore CB, Teguete I, Bah S, Dolo G, Gursel DB, Holl J, Hou L, Maiga M. Distribution of high-risk human papillomavirus in self-collected cervical vaginal samples from the general Malian population. Biochem Genet. 2024. doi: 10.1007/s10528-024-10949-5.
Shah D, Gandhi M, Kumar A, Cruz-Martins N, Sharma R, Nair S. Current insights into epigenetics, noncoding RNA interactome and clinical pharma cokinetics of dietary polyphenols in cancer chemoprevention. Crit Rev Food Sci Nutr. 2023;63(12):1755-1791. doi: 10.1080/10408398.2021.1968786.
Jiang J, Chen Y, Jiang L. Expression of CDKN2A in cervical cancer tissues and mechanism of regulating Wnt/β-catenin pathway affecting proliferation and apoptosis of SiHa cells. Hebei Medical Journal. 2021; 43 (5): 650-654. doi: 10.3969/j. issn.1002-7386.2021.05.002
Mazilu L, Suceveanu AI, Stanculeanu DL, Gheorghe AD, Fricatel G, Negru SM. Tumor microenvironment is not an ‘innocent bystander’ in the resistance to treatment of head and neck cancers (Review). Exp Ther Med. 2021;22(4):1128. doi: 10.3892/etm.2021.10562.
Ren Y, Kinghorn AD. Development of potential antitumor agents from the scaf-folds of plant-derived terpenoid lactones. J Med Chem. 2020;63(24):15410-15448. doi: 10.1021/acs.jmedchem.0c01449.
Zheng S, Lin J, Pang Z, Zhang H, Wang Y, Ma L, Zhang H, Zhang X, Chen M, Zhang X, Zhao C, Qi J, Cao L, Wang M, He X, Sheng R. Aberrant cholesterol metabolism and Wnt/β-Catenin signaling coalesce via Frizzled5 in supporting cancer growth. Adv Sci (Weinh). 2022;9(28):e2200750. doi: 10.1002/advs.202200750.
Zheng S, Guo Y, Han Q, Peng X, Sheng R, Liu S, Li Z. STING agonists and PI3Kγ inhibitor co-loaded ferric ion-punicalagin networks for comprehensive cancer therapy. Int J Biol Macromol. 2024;282(Pt 2):136776. doi: 10.1016/j.ijbiomac.2024.136776.
Matsumoto S, Kikuchi A. Wnt/β-catenin signaling pathway in liver biology and tumorigenesis. In Vitro Cell Dev Biol Anim. 2024;60(5):466-481. doi: 10.1007/s11626-024-00858-7.
Yin X, Zhu L, Feng M, Yu J, Zhan J, Liang L, Han T. Effect of continuous loading pressure on apoptosis and Wnt/β-catenin signaling pathway in nucleus pulposus cells. Chinese Journal of Tissue Engineering Research. 2020; 24 (26): 4125-4128. doi: 10.3969/j.issn.2095-4344.2762
Marongiu L, Allgayer H. Viruses in colorectal cancer. Mol Oncol. 2022;16(7):1423- 1450. doi: 10.1002/1878-0261.13100.
Chong JS, Doorbar J. Modulation of epithelial homeostasis by HPV using Notch and Wnt. Tumour Virus Res. 2024;18:200297. doi: 10.1016/j.tvr.2024.200297.
Broniarczyk J, Trejo-Cerro O, Massimi P, Kavčič N, Myers MP, Banks L. HPV-18 E6 enhances the interaction between EMI- LIN2 and SNX27 to promote WNT signaling. J Virol. 2024;98(7):e0073524. doi: 10.1128/jvi.00735-24.
Li P, Wang Y, Liu X, Zhou Z, Wang J, Zhou H, Zheng L, Yang L. Atypical antipsychotics induce human osteoblasts apoptosis via Wnt/β-catenin signaling. BMC Pharmacol Toxicol. 2019;20(1):10. doi: 10.1186/ s40360-019-0287-9.
Shu J, Du J, Wang F, Cheng Y, Chen G, Xu B, Zhang D, Chen S. Effect of 5-FU on colorectal cancer stem cell activity by targeting the Wnt/β-catenin signaling pathway. Anatomical Studies. 2022; 44 (3):203-207.
Zheng L, Pan J. The anti-malarial drug Artesunate blocks Wnt/β-catenin pathway and inhibits growth, migration and invasion of uveal melanoma Ccells. Curr Cancer Drug Targets. 2018;18(10):988-998. doi: 10.2174/1568009618666180425142653.
