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RETRACTED: Coinhibition of S1PR1 and GP130 by siRNA‐loaded alginate‐conjugated trimethyl chitosan nanoparticles robustly blocks development of cancer cells

2020· article· en· 26 citations· W3026974044 on OpenAlex· 10.1002/jcp.29781

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.

Post-publication record

Nature
Retraction
Reason
Concerns/Issues about Image;Concerns/Issues about Results and/or Conclusions;Falsification/Fabrication of Data;Investigation by Journal/Publisher;Investigation by Third Party;
Date
7/22/2024 0:00
Flagged by OpenAlex?
Yes

Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement — it reports them as false, which reads as “fine”.

Abstract

There is an interconnected network between S1P/sphingosine-1-phosphate receptor 1 (S1PR1), IL-6/glycoprotein 130 (GP130), and signal transducer and activator of transcription 3 (STAT3) signaling pathways in the tumor microenvironment, which leads to cancer progression. S1P/S1PR1 and IL-6/GP130 signaling pathways phosphorylate and activate STAT3, and it then induces the expression of S1PR1 and interleukin-6 (IL-6) in a positive feedback loop leading to cancer progression. We hypothesized that blockade of this amplification loop can suppress the growth and development of cancer cells. Therefore, we silenced STAT3 upstream molecules including the S1PR1 and GP130 molecules in cancer cells using small interfering RNA (siRNA)-loaded alginate-conjugated trimethyl chitosan (ATMC) nanoparticles (NPs). The generated NPs had competent properties including the appropriate size, zeta potential, polydispersity index, morphology, high uptake of siRNA, high rate of capacity, high stability, and low toxicity. We evaluated the effects of siRNA loaded ATMC NPs on tumor hallmarks of three murine-derived cancer cell lines, including 4T1 (breast cancer), B16-F10 (melanoma), and CT26 (colon cancer). The results confirmed the tumor-suppressive effects of combinational targeting of S1PR1 and GP130. Moreover, combination therapy could potently suppress tumor growth as assessed by the chick chorioallantoic membrane assay. In this study, we targeted this positive feedback loop for the first time and applied this novel combination therapy, which provides a promising approach for cancer treatment. The development of a potent nanocarrier system with ATMC for this combination was also another aspect of this study, which should be further investigated in cancer animal models in further studies.

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The record

Venue
Journal of Cellular Physiology
Topic
Sphingolipid Metabolism and Signaling
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
University of Alberta
Funders
Tabriz University of Medical Sciences
Keywords
STAT3Cancer cellS1PR1ChemistrySmall interfering RNACancer researchTumor microenvironmentNanocarriersCell biologyBiologyCancerSignal transductionCell cultureTransfectionDrug deliveryVascular endothelial growth factorVascular endothelial growth factor A
Has abstract in OpenAlex
yes