The PPARγ Agonist Rosiglitazone Enhances the Radiosensitivity of Human Pancreatic Cancer Cells

Abstract

Purpose

As radiation therapy is widely used for the management of pancreatic cancer, identifying novel targets to improve the radiosensitivity of cancer cells is beneficial. Rosiglitazone, a specific peroxisome proliferator-activated receptor γ (PPARγ) agonist, has an inhibitory effect on various types of cancer cells. The purpose of this paper is to investigate the effect of rosiglitazone on the radiosensitivity of pancreatic cancer cells and the potential mechanism.

Materials and Methods

PPARγ expression in pancreatic cancer and adjacent tissues was evaluated using immunohistochemistry analysis. The viability, migration and invasion ability of PANC1 and PaTu8988 cells were detected using MTT assay, scratch-wound assay and transwell invasion assay. The effect of rosiglitazone on radiosensitivity of the cells was determined using the clonogenic assay. PANC1 cells were inoculated into BALB/c mice to establish tumors. Microarray was used to investigate changes of genes involved.

Results

Higher PPARγ expression was demonstrated in pancreatic cancer tissues compared with para-carcinoma tissues. Rosiglitazone inhibited the cell viability and enhanced the radiation-induced anti-migration and anti-invasion effect. Rosiglitazone potentiated the radiosensitivity of pancreatic cancer cells and PANC1 xenografts. Microarray analysis revealed that rosiglitazone plus radiation altered the expression of multiple genes and affected multiple pathways.

Conclusion

Rosiglitazone enhances the radiosensitivity of human pancreatic cancer cells in vitro and in vivo via complex mechanisms.

Keywords:

• ionizing radiation
• pancreatic cancer
• peroxisome proliferator-activated receptor γ
• rosiglitazone
• radiosensitivity

Acknowledgments

We thank Jianyuan Song, who worked at Fujian Medical University Union Hospital for providing the human samples of paired pancreatic cancer and para-carcinoma tissues. This work is supported by the National Natural Science Foundation of China (81803166, 81673100, 81872552, 81602101 and 81703022), China Postdoctoral Science Foundation (2018M632368), Jiangsu Province Key Youth Talents Project (QNRC2016262) and Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions. Zhenyu Wang and Wenhao Shen are co-first authors for this study.

Disclosure

The authors report no conflicts of interest in this work.