Linsitinib and aspirin as the IGF1-R antagonists, inhibit regorafenib-resistant chemotherapy in colon cancer

Guo, Yu; Nasab, Entezar Mehrabi; Hassanpour, Fatemeh; Athari, Seyyed Shamsadin

doi:10.1016/j.sjbs.2021.10.019

Cited by 11 publications

(6 citation statements)

References 21 publications

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“…Therefore, there were multiple reports suggesting the association of IGF1 in crucial processes including aging, neurodegenerative diseases, and cancer. Also, IFG1 signaling interruption might halt disease progression (Feik et al, 2010;Guo et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Integrative Transcriptomics Analysis of Early-Onset and Late-Onset Colorectal Cancer

Al-Madhagi

2023

Preprint

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Colorectal cancer (CRC) is the third most common type of cancer as it accounts for approximately 7% of all cancer types. The goal of this study is to identify and analyze the differentially expressed genes (DEGs) in early-onset CRC (EOCRC) and late-onset CRC (LOCRC). The RNA-seq data was downloaded from GEO database and analyzed using GEO2R tool. This was followed by gene and pathway enrichment, detection of protein-protein interactions, predicting the governing transcriptional factors. Besides, survival rate and response to chemotherapy were also assessed. 250 DEGs were obtained, 235 down-regulated and 15 up-regulated. Extracellular structure organization, collagen-containing extracellular matrix, platelet-derived growth factor and protein digestion and absorption were the most common biological process, cellular compartment, molecular function and KEGG pathway. Moreover, ten hub genes were filtered, namely COL1A1, VWF, COL3A1, EGF, IGF1, COL1A2, ITGB3, COL11A2, COL6A1, CD163 as the top-ten hub genes while FOXC1, GATA2, YY1, TFAP2A and PPARG were predicted to be the most significant transcriptional factors controlling them. Only EGF was considered as prognostic biomarker while COL1A1 as predictive biomarker. In conclusion, the shortlisted hub genes account for the discrimination between EOCRC and LOCRC which should be further explored in-depth.

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Section: Discussionmentioning

confidence: 99%

Integrative Transcriptomics Analysis of Early-Onset and Late-Onset Colorectal Cancer

Al-Madhagi

2023

Preprint

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“…The MTT assay was utilised in order to determine whether or not the chosen formulations were cytotoxic to SW48 Cells PTEN cell lines ( 34 ). This procedure was previously described in our article.…”

Section: Methodsmentioning

confidence: 99%

Development of D-α-Tocopherol polyethylene glycol 1000 succinate fabricated nanostructural lipid carrier of sorafenib tosylate for metastatic colorectal targeting application: Stability, physical characterization, cytotoxicity, and apoptotic studies against SW48 cells PTEN

2022

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The study aimed to create D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) nanostructured lipid carriers (NLC) of sorafenib tosylate (ST) as lymphatic delivery systems (LDDS) to fight Metastatic colorectal cancer. Initially, ST-SLN, ST-NLC, and ST-LNE were formulated considering oleic acid (OA), glycerol monolinoleate (GMO), glycerol monolinoleate (GML) as solid lipid and further characterised, and tested for stability. The most stable ST-NLC was fabricated with TPGS to produce ST-TPGS-NLC and evaluated by performing in vitro drug profiling, in vitro cytotoxicity, and apoptotic studies against human female colorectal adenocarcinoma cell lines (SW48 Cells PTEN). Stability studies on three lipidic nanoparticles (ST-SLN, ST-NLC, ST-LEN) showed particle size, polydispersity index, and zeta potential ranging from 165 nm to 298 nm, 0.125 to 0.288, and -31 mV to -16 mV. At 1600 minutes, more than 80% of ST-NLC1 was released, confirming the sustained release pattern of the formulation. ST-NLC and ST-TPGS-NLC have entrapment efficiencies above 50%. Pure ST’s IC50 at 72 hr was 3.45 µg/mL, while 1.56 µg/mL was for ST-TPGS-NLC. The ST-TPGS-NLC reduced the number of livings SW48 Cells PTEN from 91% to 5%, compared to 75% to 8% of pure ST. The ST-TPGS-NLC is a promising LDDS for delivering ST for metastatic colorectal cancer.

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“…As an anti-inflammatory agent, aspirin also alleviated inflammation. 189 Berberine is a natural MET inhibitor with similar efficacy to MET-TKIs, which can be used in combination with TKIs. 190 Interestingly, PTK can be indirectly targeted.…”

Section: Mechanisms Of Tki Resistancementioning

confidence: 99%

Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective

Yang

Wang

et al. 2022

Sig Transduct Target Ther

107

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Protein tyrosine kinases (PTKs) are a class of proteins with tyrosine kinase activity that phosphorylate tyrosine residues of critical molecules in signaling pathways. Their basal function is essential for maintaining normal cell growth and differentiation. However, aberrant activation of PTKs caused by various factors can deviate cell function from the expected trajectory to an abnormal growth state, leading to carcinogenesis. Inhibiting the aberrant PTK function could inhibit tumor growth. Therefore, tyrosine kinase inhibitors (TKIs), target-specific inhibitors of PTKs, have been used in treating malignant tumors and play a significant role in targeted therapy of cancer. Currently, drug resistance is the main reason for limiting TKIs efficacy of cancer. The increasing studies indicated that tumor microenvironment, cell death resistance, tumor metabolism, epigenetic modification and abnormal metabolism of TKIs were deeply involved in tumor development and TKI resistance, besides the abnormal activation of PTK-related signaling pathways involved in gene mutations. Accordingly, it is of great significance to study the underlying mechanisms of TKIs resistance and find solutions to reverse TKIs resistance for improving TKIs efficacy of cancer. Herein, we reviewed the drug resistance mechanisms of TKIs and the potential approaches to overcome TKI resistance, aiming to provide a theoretical basis for improving the efficacy of TKIs.

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Linsitinib and aspirin as the IGF1-R antagonists, inhibit regorafenib-resistant chemotherapy in colon cancer

Cited by 11 publications

References 21 publications

Integrative Transcriptomics Analysis of Early-Onset and Late-Onset Colorectal Cancer

Integrative Transcriptomics Analysis of Early-Onset and Late-Onset Colorectal Cancer

Development of D-α-Tocopherol polyethylene glycol 1000 succinate fabricated nanostructural lipid carrier of sorafenib tosylate for metastatic colorectal targeting application: Stability, physical characterization, cytotoxicity, and apoptotic studies against SW48 cells PTEN

Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective

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