Evidence map›Paper›PMID 37062842›Full record

ArticleJournal of translational medicine2023

Brevilin A is a potent anti-metastatic CRC agent that targets the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay.

Xueying Fan, Mingjing Meng, Baoting Li, Hui Chen, Jincheng Tan, Keyang Xu, Shilin Xiao, Hiu-Yee Kwan, Zhongqiu Liu, Tao Su

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
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  3. Molecules (Basel, Switzerland) · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Xueying Fan *Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China.
Mingjing Meng *Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China.
Baoting LiGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China.
Hui ChenGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China.
Jincheng TanGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China.
Keyang XuCentre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
Shilin XiaoCentre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
Hiu-Yee KwanCentre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. hykwan@hkbu.edu.hk.
Zhongqiu LiuGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China. liuzq@gzucm.edu.cn.
Tao SuGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China. sutao@gzucm.edu.cn.
Guangzhou University of Chinese Medicine · CNHong Kong Baptist University · HKMacau University of Science and Technology · MO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMore than half of the colorectal cancer (CRC) patients will develop liver metastasis that underlies the cancer mortality. In the hepatic tumor microenvironment, the interplay between CRC cells and hepatic stellate cells (HSCs), and the activation of HSCs to become carcinoma-associated fibroblasts (CAFs) will further promote the cancer development. Nevertheless, the critical signaling molecule that involved in these processes remains unknown, which hinders the development of effective therapeutic agents for the treatment of metastatic CRC (mCRC).

methodsConditioned medium system and co-cultured system were used to examine the interplay between CRC cells and HSCs. Luminex liquid suspension chip detection and enzyme-linked immunosorbent assay were used to screen for the mediators in the conditioned medium that facilitated the CRC-HSCs interplay and HSCs-to-CAFs differentiation. Cell and animal models were used to examine whether brevilin A inhibited CRC liver metastasis via the VEGF-IL6-STAT3 axis.

resultsIn the CRC-HSCs interplay, CRC promoted HSCs-to-CAFs differentiation by releasing vascular endothelial growth factor (VEGF); and HSCs released interleukin 6 (IL6) that activated signal transducer and activator of transcription 3 (STAT3) in the CRC and hence increased the cancer metastatic potential. The functions of the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay were further validated by VEGF recombinant protein and IL6 neutralizing antibody. More importantly, brevilin A, an active compound isolated from Centipeda minima (L.) A. Br. et Aschers, targeted the VEGF-IL6-STAT3 axis in the CRC-HSCs interplay, hence significantly inhibited colorectal liver metastasis and cancer growth both in vitro and in vivo.

conclusionsWe are the first to demonstrate brevilin A possesses potent anti-mCRC effect by targeting the VEGF-IL6-STAT3 axis in the CRC-HSCs interplay. Our findings not only support the development of brevilin A as a novel therapeutic agent for mCRC treatment, but also pave the path for the development of other VEGF-IL6-STAT3 targeting therapeutic strategies.

Indexed as

Colonic NeoplasmsColorectal NeoplasmsLiver NeoplasmsRectal NeoplasmsAnimalsCell Line, TumorCrotonatesCulture Media, ConditionedHepatic Stellate CellsInterleukin-6SesquiterpenesSTAT3 Transcription FactorTumor MicroenvironmentVascular Endothelial Growth Factor Abrevilin ACrotonatesCulture Media, ConditionedInterleukin-6SesquiterpenesSTAT3 Transcription FactorVascular Endothelial Growth Factor ABrevilin ACarcinoma-associated fibroblastsHSCs-CRC interplayLiver metastases of colorectal cancerVEGF-IL6-STAT3 axis

Identifiers

PMID37062842
PMCPMC10105967
OpenAlexW4366003329

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.