Oroxin B Induces Apoptosis by Down-Regulating MicroRNA-221 Resulting in the Inactivation of the PTEN/PI3K/AKT Pathway in Liver Cancer.

Nannan Li,Hechen Wang,Xiansheng Meng,Wenxiao Men,Yibo Zheng

doi:10.3390/molecules24234384

Abstract

This study aims to investigate the anticancer effect of Oroxin B (OB) both in vitro and in vivo, and the molecular mechanism involved in microRNA-221 and the PI3K/Akt/PTEN pathway through modulation of apoptosis in Hepatocellular carcinoma (HCC). DEN-induced rats and HepG2 cells based on the microfluidic chip were employed, while the mRNA and protein expression of microRNA-221, PI3K, p-Akt and PTEN were evaluated by RT-PCR and Western blot analysis. Based on Microfluidic Chip and DEN-induced rat model, OB effectively exerts anti-liver cancer effect both in vitro and in vivo, and the expression of miR-221 in OB treated groups was significantly lower than that in the control group (** p < 0.01). The RT-PCR and Western blot results suggested the PI3K mRNA and protein in OB treated groups were both lower than those in control group and indicated the overexpression of PTEN. Therefore, OB effectively exerts anticancer effects by positively regulating the PTEN gene and then inactivating the PI3K/Akt signaling pathway through down-regulating the expression of the microRNA-221, thereby inducing apoptosis of liver cancer cells. This study offers a theoretical evidence for further development and clinical guidance of OB as an anti-tumor agent.

Highlights

Liver cancer, as a primary hepatic malignancy, is the second and sixth leading cause of cancer-related death to men and women, respectively
Oroxin B (OB) is one of the flavonoids compound in Oroxylum indicum [18]
Nagasaka et al found that chrysin from Oroxylum indicum has anti-tumorigenic activity [19]

Summary

Introduction

As a primary hepatic malignancy, is the second and sixth leading cause of cancer-related death to men and women, respectively. It is the fifth most common tumor worldwide [1]. The occurrence and development of liver cancer are related to many genes, including microRNAs. MicroRNA is a class of endogenous small RNA with a length of about 21–25 nucleotides [2]. MiR-221, whose expression raises approximately 70%–80% in liver cancer [6], could affect several cancer related pathways by modulating multiple gene targets, including the pro-apoptotic protein B-cell lymphoma

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