Copper transporter Ctr1 contributes to enhancement of the sensitivity of cisplatin in esophageal squamous cell carcinoma

Increasing evidence has demonstrated that Ctr1 plays a crucial role in the regulation of cisplatin uptake in a variety of tumors. The purpose of this study was to investigate its role in mediating cisplatin sensitivity in ESCC cells. Immunohistochemistry (IHC), In situ hybridization (ISH) and semi-quantitative RT-PCR were used to detect Ctr1 expressions in ESCC tissues. qRT-PCR and Western blot was performed to investigate the levels of Ctr1 mRNA and protein in ESCC cells. CCK-8, Flow cytometry and Transwell chamber assay were carried out to examine cell proliferation, apoptosis, migration and invasion abilities in ESCC cells. We found that ESCC tissues and cells had higher Ctr1 level than normal tissues and Het-1A cell. Ctr1 expression was correlated with histological grade, invasion depth, TNM staging and lymph node metastasis in ESCC patients. Ctr1 depletion reduced the suppressive role of proliferation, migration and invasion as well as the inductive role of cell apoptosis and Caspase-3 activity evoked by cisplatin, whereas Ctr1 upregulation combined with cisplatin exerted the synergistic role in regulation of proliferation, apoptosis, Caspase-3 activity, migration and invasion in ESCC. In conclusion, Ctr1 is implicated in ESCC development and progression and its expression may be a novel predictor for assessment of cisplatin sensitivity in ESCC.

Automated summary

Increasing evidence has shown that Ctr1 plays an important role in regulating cisplatin uptake in various tumors. This study aimed to investigate its role in mediating cisplatin sensitivity in ESCC cells. Ctr1 expression was higher in ESCC tissues and cells compared to normal tissues. Furthermore, Ctr1 depletion reduced the suppressive effects of cisplatin on proliferation, migration, invasion, and apoptosis in ESCC cells, while Ctr1 upregulation combined with cisplatin exerted synergistic effects on these cellular processes.