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Novel effects of piperlogumine on uterine fibroid tumor: An <i>in vitro</i> mouse model study


Mei Zhang
Mei Ye
Qingxiang Hou
Bin Yan
Chao Yang
Yi Yang
Li Ma

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.


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eISSN: 1596-9827
print ISSN: 1596-5996