Calcitriol enhances Doxorubicin-induced apoptosis in papillary thyroid carcinoma cells via regulating...

There is increasing evidence that vitamin D deficiency is the risk factor for multiple diseases, such as immune disorder, cardiovascular disease and cancer. Calcitriol is the active form of vitamin D with beneficial effects on anti-cancer by binding vitamin D receptor (VDR). The primary aim of this study was to investigate the role of Calcitriol on papillary thyroid carcinoma (PTC) and explore the possible mechanism. We found nuclear VDR expression in PTC samples was negatively correlated with STAT3 hyperphosphorylation that indicated worse PTC clinicopathologic characteristics. Calcitriol treatment up-regulated VDR and protein tyrosine phosphatase N 2 (PTPN2) expression, down-regulated signal transducers and activators of transcription (STAT3) phosphorylation and thereby facilitating chemotherapy drug Doxorubicin-induced apoptosis in PTC cell lines. However, the apoptosis-promoting effect of Calcitriol and Doxorubicin co-treatment was abrogated by STAT3 hyperphosphorylation, indicating suppression of STAT3 phosphorylation was essential for combined treatment of Calcitriol and Doxorubicin in PTC. Together, these results suggested that Calcitriol reinforced the sensitivity of PTC cells to Doxorubicin by regulating VDR/PTPN2/p-STAT3 signalling pathway.