Comparison of 2D and 3D cell cultures of colorectal adenocarcinoma as models for drug screening

Полозников, А. А.; Никулин, С. В.; Болотина, Л. В.; Gaisina, Irina N.; Alexeev, Boris

doi:10.1007/s11172-019-2716-8

Cited by 2 publications

(2 citation statements)

References 23 publications

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“…Inhibition of GSK-3β with other small molecule inhibitors (AR-A014418 and SB-216763) resulted in a decrease in viability of KRAS mutant CRC cell lines (SW480 and HCT116). In addition to a wide spectrum of cancer models, including glioblastoma ( Ugolkov et al, 2017 ), pancreatic ( Ding et al, 2017 ), breast ( Ugolkov et al, 2016 ), and bladder ( Kuroki et al, 2019 ) cancers, 9-ING-41 has already been tested on wild-type KRAS CRC cell line HT-29 ( Poloznikov et al, 2019 ) and recently on a panel of CRC cell lines ( Huntington et al, 2021 ). In both cases, it demonstrated an ability to decrease viability of colorectal cells.…”

Section: Discussionmentioning

confidence: 99%

“…Among GSK-3β inhibitors that are currently tested in clinical trials, 9-ING-41 was selected as it was recently granted fast-track designation for treatment of patients with pancreatic cancer by the U.S. Food and Drug Administration (FDA). This small molecule was previously tested on several CRC cell lines harboring mutant and wild-type KRAS genes as a single drug and demonstrates superior growth inhibition activity toward oxaliplatin-resistant cells ( Poloznikov et al, 2019 ; Huntington et al, 2021 ). Primary CRC organoids were selected due to their ability to preserve genetic and histopathological features of the original tumor and to predict clinical response ( van de Wetering et al, 2015 ; Fujii et al, 2016 ; Tiriac et al, 2018 ; Nikulin et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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9-ING-41, a Small Molecule Inhibitor of GSK-3β, Potentiates the Effects of Chemotherapy on Colorectal Cancer Cells

et al. 2021

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Colorectal cancer (CRC) is one of the most common and lethal types of cancer. Although researchers have made significant efforts to study the mechanisms underlying CRC drug resistance, our knowledge of this disease is still limited, and novel therapies are in high demand. It is urgent to find new targeted therapy considering limited chemotherapy options. KRAS mutations are the most frequent molecular alterations in CRC. However, there are no approved K-Ras targeted therapies for these tumors yet. GSK-3β is demonstrated to be a critically important kinase for the survival and proliferation of K-Ras–dependent pancreatic cancer cells. In this study, we tested combinations of standard-of-care therapy and 9-ING-41, a small molecule inhibitor of GSK-3β, in CRC cell lines and patient-derived tumor organoid models of CRC. We demonstrate that 9-ING-41 inhibits the growth of CRC cells via a distinct from chemotherapy mechanism of action. Although molecular biomarkers of 9-ING-41 efficacy are yet to be identified, the addition of 9-ING-41 to the standard-of-care drugs 5-FU and oxaliplatin could significantly enhance growth inhibition in certain CRC cells. The results of the transcriptomic analysis support our findings of cell cycle arrest and DNA repair deficiency in 9-ING-41–treated CRC cells. Notably, we find substantial similarity in the changes of the transcriptomic profile after inhibition of GSK-3β and suppression of STK33, another critically important kinase for K-Ras–dependent cells, which could be an interesting point for future research. Overall, the results of this study provide a rationale for the further investigation of GSK-3 inhibitors in combination with standard-of-care treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

9-ING-41, a Small Molecule Inhibitor of GSK-3β, Potentiates the Effects of Chemotherapy on Colorectal Cancer Cells

et al. 2021

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Study on the Toxicity of Calix[4]- and [6]-Arenes and their Sulfated Derivatives in Two- and Three-Dimensional Cell Cultures of Colorectal Adenocarcinoma

Никулин

Alekseev

Горбунов

et al. 2021

Biiotehnologiâ (Mosk.)

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A comparative study of the toxicity of two unsubstituted calixarenes consisting of 4 and 6 phenolic fragments, as well as their p-sulfated derivatives, was carried out on the HT-29 colorectal adenocarcinoma cells cultured in two-dimensional (2D) and three-dimensional (3D) formats. It was shown that both unsubstituted calixarenes decrease the viability of tumor cells; calix[4]arene and calix[6]arene exhibited a cytostatic and a cytotoxic effect, respectively. Sulfated derivatives of calixarenes did not have a pronounced toxic effect on HT-29 cells. However, due to their high hydrophilicity and the ability to form adducts with various therapeutic molecules, they can be used for delivery of anticancer drugs. calixarenes, cytotoxicity, HT-29 cells, 2D cell culture, 3D cell culture The work was financially supported by the Russian Science Foundation (project no. 19-15-00397).

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Comparison of 2D and 3D cell cultures of colorectal adenocarcinoma as models for drug screening

Cited by 2 publications

References 23 publications

9-ING-41, a Small Molecule Inhibitor of GSK-3β, Potentiates the Effects of Chemotherapy on Colorectal Cancer Cells

9-ING-41, a Small Molecule Inhibitor of GSK-3β, Potentiates the Effects of Chemotherapy on Colorectal Cancer Cells

Study on the Toxicity of Calix[4]- and [6]-Arenes and their Sulfated Derivatives in Two- and Three-Dimensional Cell Cultures of Colorectal Adenocarcinoma

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