Targeting the differentiation of gastric cancer cells (KATO‑III) downregulates epithelial‑mesenchymal and cancer stem cell markers

Shah,Shahid; Pocard,Marc; Mirshahi,Massoud

doi:10.3892/or.2019.7198

Targeting the differentiation of gastric cancer cells (KATO‑III) downregulates epithelial‑mesenchymal and cancer stem cell markers

Authors:
- Shahid Shah
- Marc Pocard
- Massoud Mirshahi
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Affiliations: University of Sorbonne Paris Cité‑Paris 7, Lariboisière Hospital, INSERM U965, 75010 Paris, France
Published online on: June 12, 2019 https://doi.org/10.3892/or.2019.7198
Pages: 670-678
Copyright: © Shah et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to analyze the acquisition of the differentiated phenotype in the human gastric signet ring cell adenoma cancer KATO‑III cell line in vitro. The morphology of KATO‑III cells was explored by microcinematography. Different cytokines secreted by both adherent and non‑adherent KATO‑III cells into medium were observed. The cancer stem cell phenotypes were identified by reverse transcription‑quantitative polymerase chain reaction using primers (E‑Cad, Slug, Snail, vimentin, NANOG, NESTIN, OCT3/4 and C‑X‑C motif chemokine receptor 4) or antibodies [cluster of differentiation (CD)90 and CD117] by flow cytometry (FACS). The influence of the induction media for the differentiation of mesenchymal cells was studied through viability and proliferation assays, by evaluating gene expression and the expression of markers via FACS. Cell viability and cell cycle distribution were evaluated following the treatment of KATO‑III with acetyl salicylic acid and using the induction media as an inhibitor of epithelial‑mesenchymal transition (EMT) and heparanase. A total of 3 phenotypes of KATO‑III were observed (adherent, non‑adherent and cell cluster), which have internal potential for cell transition into one of the other phenotypes. KATO‑III was differentiated into adipocyte‑, chondrocyte‑, osteocyte‑ and neurocyte‑like cells by the induction media. Identification of the induced cells was conducted using cell dyes. Reduced mRNA expression of EMT‑associated molecules, stem cell markers and heparanase was observed with acetyl salicylic acid and induction media. An inhibitory effect of acetyl salicylic acid and the induction media was also noted in regard to cell proliferation. In addition, acetyl salicylic acid induced G0/G1 phase cell cycle arrest in KATO‑III cells. In conclusion, the induction of the differentiation of cancer stem cells into non‑proliferating cells offers the possibility for novel drug design to overcome the issues associated with metastasis, drug resistance and systemic toxicity with improved therapeutic efficacy.

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