Hydroxypropyl-β-Cyclodextrin-Complexed Resveratrol Enhanced Antitumor Activity in a Cervical Cancer Model: In Vivo Analysis.

Xincai Hao,Ming Sang,Pan Fu,Haizhen Zhu,Lixia Xie,Xuanbin Wang,Nan Jiang,Xiaodong Sun

doi:10.3389/fphar.2021.573909

Abstract

Trans-resveratrol (RES) exhibits a wide range of biological activities. Various methodological approaches have been established to improve the pharmacokinetic properties of RES. Moreover, additional in vivo studies are required to support clinical application. In this study, RES/HP-β-CD (RHSD) inclusion complex was prepared and characterized by FTIR, PXRD, DSC and NMR data. The effect and potential mechanism of RHSD against cervical cancer were investigated in a mouse xenograft tumor model by qPCR assay, Western blot assay, and immunohistochemical assay. Results showed that RHSD significantly decreased tumor growth compared with free RES, while the effect of preventing tumor growth was more prominent in vivo. Notably, RHSD could inhibit tumor development by suppressing the expression of HPV E6 and E7 oncogenes and upregulating P53 and Rb1 protein in cervical cancer. These findings demonstrated that RHSD was safe and potential for development of a new oral administration drug to treat cervical cancer.

Highlights

Cervical cancer is the second most common cancer of global cancer deaths among women (Ferlay et al, 2015)
About 100% of the RES of complex amount dissolved within 10–20 min, while Less than 3% free RES was dissolved within 120 min
The disappearance and shift characteristics of the spectrum revealed the formation of the RHSD inclusion complex

Summary

Introduction

Cervical cancer is the second most common cancer of global cancer deaths among women (Ferlay et al, 2015). High-risk HPV E6 and E7 proteins have been shown to promote tumorigenesis by promoting cell immortality and migration, changing cell cycle and apoptosis control, and avoiding host immune surveillance (Thomas and Chiang, 2005; Liu et al, 2009; De Sanjose et al, 2010; Ghittoni et al, 2010; Au Yeung et al, 2011). This cellular response is related to the regeneration of P53 and Rb1 anti-proliferative proteins (Scheffner et al, 1990; Dyson et al, 1992; Heck et al, 1992; Huibregtse et al, 1993; Taghizadeh et al, 2019). The current cancer prevention and treatment methods in developing countries have failed to significantly reduce cervical cancer

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