Zoledronic acid exhibits radio-sensitizing activity in human pancreatic cancer cells via inactivation of STAT3/NF-κB signaling.

Although pancreatic cancer is typically radio-sensitive, local treatment failure and metastasis are commonly caused by the development of resistance to radiotherapy. In the current study, the radio-sensitizing actions of zoledronic acid (ZOL) on pancreatic cancer cells were investigated. Three human pancreatic cancer cell lines were exposed to ZOL, ionizing radiation (IR), or a combination of both, and the effects of the respective drug regimens on cell proliferation and invasion were examined. Combined treatment with low doses of ZOL plus IR efficiently increased cell death and attenuated cell invasion compared with the individual use of ZOL or IR. These effects of ZOL were associated with inactivation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB). Collectively, these data suggest that ZOL in combination with IR is a promising therapeutic strategy for enhancing radio-sensitivity in pancreatic cancer cells via downregulation of the STAT3/NF-κB signaling pathway.