Paeoniflorin Inhibits Migration and Invasion of Human Glioblastoma Cells via Suppression Transforming Growth Factor \u03b2-Induced Epithelial\u2013Mesenchymal Transition

Zhaotao Wang,Zhi Liu,Weiqiang Jia,Ruxiang Xu,Guoyong Yu,Ru-En Liu,Xiaohu Nie

doi:10.1007/s11064-018-2478-y

Abstract

Paeoniflorin (PF) is a polyphenolic compound derived from Radix Paeoniae Alba thathas anti-cancer activities in a variety of human malignancies including glioblastoma. However, the underlying mechanisms have not been fully elucidated. Epithelial to mesenchymal transition (EMT), characterized as losing cell polarity, plays an essential role in tumor invasion and metastasis. TGFβ, a key member of transforming growth factors, has been demonstrated to contribute to glioblastoma aggressiveness through inducing EMT. Therefore, the present studies aim to investigate whether PF suppresses the expression of TGFβ and inhibits EMT that plays an important role in anti-glioblastoma. We found that PF dose-dependently downregulates the expression of TGFβ, enhances apoptosis, reduces cell proliferation, migration and invasion in three human glioblastoma cell lines (U87, U251, T98G). These effects are enhanced in TGFβ siRNA treated cells and abolished in cells transfected with TGFβ lentiviruses. In addition, other EMT markers such as snail, vimentin and N-cadherin were suppressed by PF in these cell lines and in BALB/c nude mice injected with U87 cells. The expression of MMP2/9, EMT markers, are also dose-dependently reduced in PF treated cells and in U87 xenograft mouse model. Moreover, the tumor sizes are reduced by PF treatment while there is no change in body weight. These results indicate that PF is a potential novel drug target for the treatment of glioblastoma by suppression of TGFβ signaling pathway and inhibition of EMT.

Highlights

Zhaotao Wang and Zhi Liu have contributed .Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Affiliated Bayi Brain Hospital, General ArmyHospital, Southern Medical University, Beijing, People’s Republic of ChinaDepartment of Neurosurgery, Peking UniversityPeople’s Hospital, Peking University, Beijing, Nanchang University Medical College, Nanchang, Jiangxi, Huzhou Central Hospital, Zhejiang, Vol:.(1234567890)Malignant gliomas are the most common and deadly brain tumors
We found that PF dose-dependently downregulates the expression of TGFβ, enhances apoptosis, reduces cell proliferation, migration and invasion in three human glioblastoma cell lines (U87, U251, T98G)
We examined the effects of PF on cell proliferation, apoptosis, migration and invasion in human glioblastoma cell lines

Summary

Introduction

Zhaotao Wang and Zhi Liu have contributed . Southern Medical University, Beijing, People’s Republic of China. People’s Hospital, Peking University, Beijing, Nanchang University Medical College, Nanchang, Jiangxi, Huzhou Central Hospital, Zhejiang, Vol:.(1234567890). Malignant gliomas are the most common and deadly brain tumors. Glioblastoma, characterized as rapid growth and highly invasiveness, is the most malignant in all glioma pathological types [1,2,3]. A variety of therapeutic approaches have been developed, including surgery, chemotherapy, radiotherapy or combined modalities, the average survival time of patients diagnosed with glioblastoma is seldom more than 15 months [4, 5]. It is urgent to discover new agents to cure the glioblastoma

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