Mei Zhang1,
Mei Ye2,
Qingxiang Hou2,
Bin Yan3,
Chao Yang4,
Yi Yang2,
Li Ma2
1JinZhou Medical University, PLA Rocket Force Characteristic Medical Centre Graduate Training Base, Beijing 100088;
2Department of Obstetrics and Gynaecology;
3Department of Critical Care Medicine;
4Blood Transfusion Department, The PLA Rocket Force Characteristic Medical Center, Beijing 100088, China.
For correspondence:- Li Ma
Email: mali.rocketforce@gmail.com Tel:+861066343360
Accepted: 16 June 2021
Published: 29 July 2021
Citation:
Zhang M, Ye M, Hou Q, Yan B, Yang C, Yang Y, et al.
Novel effects of piperlogumine on uterine fibroid tumor: An in vitro mouse model study. Trop J Pharm Res 2021; 20(7):1433-1439
doi:
10.4314/tjpr.v20i7.16
© 2021 The authors.
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Abstract
Purpose: To investigate the in vivo anti-tumor effect of piperlongumine (PL) in a mouse model of leiomyoma xenograft and in leiomyoma cell lines.
Methods: The anti-proliferative effect of PL on ELT-3 cells was determined using MTT assay. Human and rat leiomyoma cells were used for the in vitro investigations. Rat leiomyoma cell lines were treated with various PL concentrations (50 - 100 μM)) for 48 h. Immunodeficient mice were subcutaneously injected with varying doses of estrogen or progesterone, and xenografted with explanting human leiomyoma cells in in vivo experiments. Proliferation assessment, caspase-3 expression, analysis of tumour samples, insertion of pellets of oestrogen-progesterone, tissue treatment and implantation, and immuno-histochemical analyses were carried out using appropriate procedures.
Results: Piperlongumine (PL) produced significant and dose-dependent increase in caspase-3 activity, apoptosis and suppression of cellular proliferation (p < 0.01). Moreover, Western blot data demonstrated that PL decreased phosphorylation of Akt signaling pathway. The results showed significant (p < 0.01) inhibition of tumor growth, including in ultra-sound in vivo studies, when compared with 30-day control and animals treated with PL (100 μg/g). Immuno-histochemical studies showed that PL decreased the expression of proliferation marker in xenografted tumor tissues (p < 0.02).
Conclusion: These results suggest that piperlongumine has potentials as a therapeutic agent for the management of uterine leiomyoma. However, additional studies using human cell lines are required to understand its genetic and molecular mechanisms.
Keywords: Uterine fibroids, Immune-deficiencies, Xenograft animal model, Tumor, Leiomyoma cells, Estrogen, Progesterone