Evidence map›Paper›PMID 39223679›Full record

ArticleHereditas2024

Combination of arsenic trioxide and apatinib synergistically inhibits small cell lung cancer by down-regulating VEGFR2/mTOR and Akt/c-Myc signaling pathway via GRB10.

Yao Yu, Yu Shang, Si Shi, Yaowu He, Wenchao Shi, Menghan Wang, Qi Wang, Dandan Xu, Ce Shi, Hong Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hereditas, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–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

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

5 citing papers in PubMed.

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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.

Yao Yu *Harbin Medical University, Harbin, Heilongjiang Province, China.
Yu Shang *Department of Respiration, The First Hospital of Harbin, Harbin, Heilongjiang Province, China.
Si Shi *Harbin Medical University, Harbin, Heilongjiang Province, China.
Yaowu HeHarbin Medical University, Harbin, Heilongjiang Province, China.
Wenchao ShiHarbin Medical University, Harbin, Heilongjiang Province, China.
Menghan WangHarbin Medical University, Harbin, Heilongjiang Province, China.
Qi WangHarbin Medical University, Harbin, Heilongjiang Province, China.
Dandan XuHarbin Medical University, Harbin, Heilongjiang Province, China.
Ce ShiNHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University (HMU), Harbin, Heilongjiang Province, China. shice@hrbmu.edu.cn.
Hong ChenHarbin Medical University, Harbin, Heilongjiang Province, China. yy573879253@126.com.

Funding

Wu Jieping Medical Foundation 320.6750.2021-16-24
6 · The paper itself

Abstract

backgroundSmall cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes.

methodsThe current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC.

resultsIn combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3β/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues.

conclusionsSynergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.

Indexed as

Arsenic TrioxideCell ProliferationDrug SynergismLung NeoplasmsProto-Oncogene Proteins c-aktPyridinesSignal TransductionSmall Cell Lung CarcinomaTOR Serine-Threonine KinasesVascular Endothelial Growth Factor Receptor-2AnimalsAntineoplastic AgentsCell Line, TumorCell MovementDown-RegulationGene Expression Regulation, NeoplasticAntineoplastic AgentsapatinibArsenic TrioxideGRB10 Adaptor ProteinKDR protein, humanMTOR protein, humanMYC protein, humanProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycPyridinesTOR Serine-Threonine KinasesVascular Endothelial Growth Factor Receptor-2ApatinibArsenic trioxideGRB10Small cell lung cancerSynergistic effect

Identifiers

PMID39223679
PMCPMC11367874

What Socratic holds

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LicenceCC BY
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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 Socratic graph.