OncoTargets and Therapy (Jun 2019)
Zoledronic acid exhibits radio-sensitizing activity in human pancreatic cancer cells via inactivation of STAT3/NF-κB signaling
Abstract
Yanjie You*,1 Qiang Wang,2,* Haijun Li,3,* Yuhong Ma,1 Yanhong Deng,1 Zhengcai Ye,4 Feihu Bai11Department of Gastroenterology, Ningxia Hui Autonomous Region People’s Hospital, Yinchuan, Ningxia Hui Autonomous Region 750021, People’s Republic of China; 2Department of Science and Education, Ningxia Hui Autonomous Region People’s Hospital, Yinchuan 750021, People’s Republic of China; 3Department of Radiation Oncology, The Second People’s Hospital of Neijiang, Neijiang, Sichuan 641003, People’s Republic of China; 4Endoscopy Center, Ningxia Hui Autonomous Region People’s Hospital, Yinchuan 750021, People’s Republic of China*These authors contributed equally to this work Background: 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.Materials and methods: 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.Results: 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).Conclusion: 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.Keywords: pancreatic cancer, radio-resistance, zoledronic acid, radio-sensitizing effects
