Abstract
The objective of this study was to investigate the effect of human esophageal fibroblast-derived exosomal miR-21 on cisplatin sensitivity against esophageal squamous EC9706 cells. EC9706 cells were co-cultured indirectly with human esophageal fibroblasts (HEF) or miR-21 mimics transfected-HEF in the transwell system. The exosomes in HEF-culture conditioned medium were extracted by differential ultracentrifugation. EC9706 cells were co-cultured with HEF-derived exosomes directly. The cisplatin sensitivity against EC9706 cells was revealed via half maximal inhibitory concentration (IC50) values using MTT assay. The expressions of miR-21, programmed cell death 4 (PDCD4) mRNA, and gene of phosphate and tension homology deleted on chromosome ten (PTEN) mRNA were determined by qRT-PCR. The changes of the protein level were detected using western blot assay. IC50 values of cisplatin against EC9706 cells were increased after EC9706 cells were co-cultured with either HEF or exosomes derived from miR-21 mimics-transfected HEF. Following the increased level of miR-21, the mRNA expression and protein levels of PTEN and PDCD4 were decreased in EC9706 cells. The cisplatin sensitivity to EC9706 cells was reduced by HEF-derived exosomal miR-21 through targeting PTEN and PDCD4. This study suggested that non-tumor cells in the tumor micro-environment increased the tumor anti-chemotherapy effects through their exosomes.
Highlights
Esophageal cancer (EC) is a common malignant tumor in the digestive system, ranking 6th in global incidence of the most common cause of death in cancer patients
The content of programmed cell death 4 (PDCD4) mRNA and PTEN mRNA were significantly decreased in EC9706 cells transfected with miR-21-5p mimics (Po0.05), and significantly increased in EC9706 cells transfected with miR-inhibitor (Figure 1C and D)
The overexpression of miR-21-5p decreased the expression of PDCD4 protein (Po0.05) and PTEN protein (Po0.05) in EC9706 cells (Figure 1F and G), suggesting that the overexpression of miR-21-5p can inhibit the expression of PDCD4 and PTEN protein in EC9706 cells and can decrease the cisplatin sensitivity to EC9706 cells
Summary
Esophageal cancer (EC) is a common malignant tumor in the digestive system, ranking 6th in global incidence of the most common cause of death in cancer patients. Esophageal squamous cell carcinoma (ESCC) accounts for 70% cases of EC globally, and remains a common pathological type highly prevalent in northern China, called ‘‘esophageal cancer belt’’ (1). Chemotherapy remains the first-line approach for EC treatment and plays an important role in limiting tumor growth before surgery and radiotherapy. Great progress has been made in chemo-therapeutics, its failure due to drug-resistant tumors still occurs frequently in clinical practice. When cisplatin is used to clinically treat EC for a long time, EC cells tend to become resistant to cisplatin treatment (2).
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Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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