Swertiamarin suppresses proliferation, migration, and invasion of hepatocellular carcinoma cells <em>via</em> negative regulation of FRAT1

Abstract

Studies have shown that swertiamarin (STM) has multiple biological activities, but its anti-tumour effects and molecular mechanisms are still unclear. The present research aimed to validate the STM’s impacts on the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells, and to study its potential mechanism. Two HCC cell lines were treated with STM. Tumour growth was observed by the mouse tumour xenografts model. HCC cell lines stably expressing T-cell lymphomas 1 (FRAT1) were generated by lentivirusmediated overexpression. Cell viability, proliferation, migration, and invasion were observed using Cell Counting Kit-8 (CCK8), the xCELLigence Real-Time Cell Analyzer system (RTCA), and transwell analysis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to observe the expression of FRAT1 and proteins related to the Wnt/β-catenin signalling pathway. Tumour growth was inhibited by STM in vivo. STM suppressed the proliferation, migration, and invasion of HCC cells. STM negatively regulated FRAT1 expression, whereas overexpressed FRAT1 blocked the anti-tumour function of STM. The results revealed that STM suppressed the FRAT1/Wnt/β-catenin signalling pathway. The findings of this study provide new insights into investigation of therapeutic strategies against HCC.

FRAT1 promotes the angiogenic properties of human glioblastoma cells via VEGFA

“…To the best of our knowledge, the role of FraT1 and VeGFa in glioma, prognosis and diagnosis, was investigated for the first time in the present study, based on using the TcGa database and physiological and biochemical methods. The results demonstrated that the expression of FraT1 and VeGFa in pan-cancer was similar to that seen in certain previous studies (62,63). Furthermore, FraT1 and VeGFa mrna expression levels were significantly increased in GBMLGG compared with normal tissues.…”

A Review on the Ethnomedicinal Usage, Phytochemistry, and Pharmacological Properties of Gentianeae (Gentianaceae) in Tibetan Medicine

“…Waltonitone isolated from G. waltonii induces tumor cell cycle arrest through regulating Akt and ERK1/2 pathways, thereby inhibiting tumor cell growth [118]. Swertiamarin had certain inhibitory and pro-apoptotic effects on hepatocellular carcinoma cells in vitro [119]. Swertiamarin and mangiferin from S. davidii are the main active substances that inhibit growth and induce apoptosis in HepG2 human liver cancer cells [120].…”

The Traditional Uses, Phytochemistry, Pharmacology, Toxicology, and Clinical Uses of Metagentiana Rhodantha (Franch.) T.N.Ho and S.W.Liu, an Ethnomedicine in Southwest China

“…Secoiridiods are characteristic substances of MR, while their contents are very low. Studies have indicated that secoiridiod glycosides possess wide biological activities such as anti-inflammatory and immunoregulatory ( Saravanan et al, 2014a ; Saravanan et al, 2014b ; Wang et al, 2019a ), analgesic ( Liu et al, 2016 ; Garrido-Suárez et al, 2020 ), anti-tumor ( Tang et al, 2019 ; Xiao et al, 2020 ) hepatoprotective ( Shao et al, 2017 ; Wu et al, 2017 ), hypoglycemic ( Vaidya et al, 2013a ; Dhanavathy, 2015 ; Vaidya et al, 2012 ; Vaidya et al, 2009 ), neuroprotective ( Wang et al, 2019b ; Wu et al, 2019 ) effects.…”

“…Recently, it has revealed that SWM suppresses proliferation, migration, and invasion of HCCs ( Xiao et al, 2020 ). The cell viability was assayed by the CCK8 method.…”

“…Nowadays, it has revealed that the compounds or extracts from MR exhibit anti-inflammatory ( Somani et al, 2016 ; Qu et al, 2017 ), antioxidant ( Saha et al, 2016 ; Mahalanobish et al, 2019 ), analgesic ( Dar et al, 2005 ; Garrido-Suárez et al, 2014 ), antitumor ( Takeda et al, 2016 ; Deng et al, 2018 ; Tang et al, 2019 ; Xiao et al, 2020 ), hepatoprotective ( Das et al, 2012 ; Jain et al, 2013 ), and other effects. However, the pharmacological research mainly focuses on the characteristic compounds especially MAF but not the extracts.…”