Modulation of VDR and Cell Cycle-Related Proteins by Vitamin D in Normal Pancreatic Cells and Poorly Differentiated Metastatic Pancreatic Cancer Cells

Abstract

Many in vitro studies support the general idea that vitamin D plays a protective role against cancer. Increased doses of vitamin D dietary supplements have been widely used for the potential anticancer benefits of vitamin D. However, despite substantial epidemiological research, there are no clear conclusive data to support the use of vitamin D as a cancer preventive or treatment agent. In the, herein, reported study, we checked the effects of 1,25-dihydroxyvitamin D₃ concentrations on the expression level of the vitamin D receptor (VDR) and cell cycle-related proteins CDKN1A (p21) and CDK1 in pancreatic cells and Panc-1 pancreatic cancer (PC) cells. We found that VDR, CDKN1A, and CDK1 were upregulated by an increase in 1,25-dihydroxyvitamin D₃ concentration in normal pancreatic cells but not in the advanced cancer cell line Panc-1 from poorly differentiated metastatic PC cells. A further increase in 1,25-dihydroxyvitamin D₃ concentration above the physiological range significantly downregulated the expression of VDR, indicating that VDR is modulated by VDR levels to maintain normal functioning during dramatic variations in vitamin D concentration. By increasing the level of cell cycle inhibitory and promoting proteins p21 and CDK1, vitamin D theoretically has both preventive and promoting effects on pancreatic cell division.

Acknowledgments

This work was performed at the Neurobiology Institute of Taishan Medical University, Tai’an, China.

Disclosure Statement

The authors have no conflict of interest to declare.

Additional information

Funding

It was financially supported by the Tai'an Science and Technology Development Plan (201540702) and Taishan Medical University.