Combining use of Phillyrin and autophagy blocker alleviates laryngeal squamous cell carcinoma via AMPK/mTOR/p70S6K signaling.

Da-Hua Wang,Qing He,Xi He

doi:10.1042/bsr20190459

Abstract

Phillyrin (PHN), one of the major active constituents of Forsythia suspensa and F. koreana, has been reported to produce antioxidant, antibacterial, anti-obesity and anti-inflammatory effects. However, no study has demonstrated the role of PHN in laryngeal squamous cell carcinoma (LSCC). We aimed to investigate the effects of PHN on the proliferation and apoptosis of HEp-2 cells. In the present study, PHN alone showed little effect on HEp-2 cell proliferation and apoptosis. Subsequent tests showed that PHN could largely enhance the level of autophagy on HEp-2 cells. Combining use of PHN and autophagy blockers including 3-methyladenine (3-MA) and chloroquine (CQ) significantly inhibited HEp-2 cell proliferation in a dose- and time-dependent manner and induced apoptosis after 24 h in a dose-dependent manner. Additionally, we found that the possible underlying molecular mechanism of PHN-induced autophagy might be through the AMPK/mTOR/p70S6K signaling pathway. Taken together, our study indicates that combining use of PHN and autophagy blockers may serve as a novel strategy in LSCC treatment.

Highlights

Laryngeal squamous cell carcinoma (LSCC) is regarded as one of the most common carcinomas of the head and neck [1,2]
Surgery is regarded as the primary treatment for LSCC
Nonsurgical options like radiation and chemotherapy have emerged as viable options [27]

Summary

Introduction

Laryngeal squamous cell carcinoma (LSCC) is regarded as one of the most common carcinomas of the head and neck [1,2]. The therapeutic effect is moderate in early-stage LSCC, yet it is not as good in advanced stages, despite improvements in the management and treatment of the disease [3,4]. It is crucial and urgent for us to gain a better understanding of the molecular mechanisms of LSCC progression and the identification of more effective targets to improve therapeutic efficacy for this disease. The anti-inflammatory effects of PHN have been increasingly studied recently. No report was available on the anti-tumor effect of PHN

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