Evidence map›Paper›PMID 40467915›Full record

ArticleDigestive diseases and sciences2025

The Combination of PF-543 and TRAIL Effectively Induces Apoptotic Cell Death and Inhibits Stem Cell-Like Properties Through the SPHK1/S1PR1/STAT3 Pathway in TRAIL-Resistant Colorectal Cancer Cells.

Se Lim Kim, Min Woo Shin, Byung Chul Jin, Seung Young Seo, Sang Wook Kim

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Article in Digestive diseases and sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

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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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Se Lim KimDepartment of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University Medical School, 20, Geonji-ro, Deokjin-gu, Jeonju, Jeonbuk, 54907, Republic of Korea.
Min Woo ShinDepartment of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University Medical School, 20, Geonji-ro, Deokjin-gu, Jeonju, Jeonbuk, 54907, Republic of Korea.
Byung Chul JinDepartment of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University Medical School, 20, Geonji-ro, Deokjin-gu, Jeonju, Jeonbuk, 54907, Republic of Korea.
Seung Young Seo *Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University Medical School, 20, Geonji-ro, Deokjin-gu, Jeonju, Jeonbuk, 54907, Republic of Korea. bear7905@jbnu.ac.kr.
Sang Wook Kim *Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University Medical School, 20, Geonji-ro, Deokjin-gu, Jeonju, Jeonbuk, 54907, Republic of Korea.

Funding

National Research Foundation of Korea (NRF) grant funded by the Korea government 2022R1F1A1064215
6 · The paper itself

Abstract

purposeTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cell types. Although TRAIL can directly trigger cell death, cancer cells may acquire resistance to its apoptotic effects during treatment. Sphingosine kinase 1 (SPHK1) is a key regulator of cancer progression and resistance to therapy. In this study, we determined whether combining TRAIL with PF-543, a specific SPHK1 inhibitor, could circumvent TRAIL resistance in previously established TRAIL-resistant colorectal cancer cells (HCT116-TR cells).

methodsHCT116-TR cells were treated with TRAIL and/or PF-543. Apoptotic cell death and signaling pathways were evaluated using MTT assay, colony formation assay, and flow cytometry analysis. Cell aggressiveness and cancer stemness were assessed through wound healing assay, Matrigel-coated Transwell assay, and tumorsphere formation assay. The underlying molecular mechanisms were examined by Western blotting.

resultsCombined treatment with PF-543 significantly enhanced TRAIL-induced apoptosis in HCT116-TR cells and exhibited a synergistic effect. Mechanistically, PF-543 sensitized HCT116-TR cells to TRAIL by activating the mitochondrial apoptosis pathway. Moreover, PF-543 increased TRAIL sensitivity by regulating DcR1 and DR5 through the SPHK1/S1PR1/STAT3 pathway. In addition, combination treatment reduced the aggressiveness and cancer stemness of HCT116-TR cells by modulating the epithelial-mesenchymal transition (EMT) pathway as well as cancer stemness markers.

conclusionWe identified the molecular mechanisms underlying acquired TRAIL resistance in CRC cells and suggest that targeting SPHK1 represents a potential strategy to overcome TRAIL resistance and inhibit CRC metastasis.

Indexed as

ApoptosisColorectal NeoplasmsDrug Resistance, NeoplasmNeoplastic Stem CellsPhosphotransferases (Alcohol Group Acceptor)PyrrolidinesSTAT3 Transcription FactorTNF-Related Apoptosis-Inducing LigandEpithelial-Mesenchymal TransitionHCT116 CellsHumansMethanolSignal TransductionSphingosine-1-Phosphate ReceptorsSphingosine KinaseSulfonesMethanolPF-543Phosphotransferases (Alcohol Group Acceptor)PyrrolidinesS1PR1 protein, humanSphingosine-1-Phosphate ReceptorsSphingosine KinaseSTAT3 protein, humanSTAT3 Transcription FactorSulfonesTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanApoptosisCancer stem cellsChemoresistanceColorectal cancerInvasionPF-543S1PR1SPHK1STAT3TRAIL

Identifiers

PMID40467915

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