Paclitaxel‑resistant gastric cancer MGC‑803 cells promote epithelial‑to‑mesenchymal transition and chemoresistance in paclitaxel‑sensitive cells via exosomal delivery of miR‑155‑5p

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Abstract

Paclitaxel is a first‑line chemotherapeutic agent for gastric cancer; however, resistance limits its effectiveness. Investigation into the underlying mechanisms of paclitaxel resistance is urgently required. In the present study, a paclitaxel‑resistant gastric cancer cell line (MGC‑803R) was generated with a morphological phenotype of epithelial‑to‑mesenchymal transition (EMT) and increased expression levels of microRNA (miR)‑155‑5p. MGC‑803R cell‑derived exosomes were effectively taken up by paclitaxel‑sensitive MGC‑803S cells, which exhibited EMT and chemoresistance phenotypes. miR‑155‑5p was enriched in MGC‑803R‑exosomes and could be delivered into MGC‑803S cells. miR‑155‑5p overexpression in MGC‑803S cells via transfection with mimics resulted in similar phenotypic effects as treatment with MGC‑803R exosome and increased miR‑155‑5p content in MGC‑803S exosomes, which then capable of inducing the malignant phenotype in the sensitive cells. GATA binding protein 3 (GATA3) and tumor protein p53‑inducible nuclear protein 1 (TP53INP1) were identified as targets of miR‑155‑5p. Exosomal miR‑155‑5p inhibited these targets by directly targeting their 3' untranslated regions. Knockdown of miR‑155‑5p was observed to reverse the EMT and chemoresistant phenotypes of MGC‑803R cells, potentially via GATA3 and TP53INP1 upregulation, which inhibited MGC‑803R‑exosomes from inducing the malignant phenotype. These results demonstrated that exosomal delivery of miR‑155‑5p may induce EMT and chemoresistant phenotypes from paclitaxel‑resistant gastric cancer cells to the sensitive cells, which may be mediated by GATA3 and TP53INP1 suppression. Targeting miR‑155‑5p may thus be a promising strategy to overcome paclitaxel resistance in gastric cancer.

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