Inhibition of JAK2/STAT3 signaling pathway increases radiotherapy sensitivity of pancreatic cancer cells in vitro

Pancreatic cancer is a gastrointestinal cancer with high mortality. Radiotherapy is an important pancreatic cancer therapy; however, cancer cell resistance to radiotherapy is the major reason for treatment failure. The JAK2／STAT3 (Janus kinase signal transducers 2 and activator of transcription 3) signaling pathway is closely related to the incidence and development of pancreatic cancer, and may be associated with pancreatic cancer resistance to radiotherapy. This study investigated the differences in JAK2 expression in pancreatic cancer irradiated with different doses, also researched the differences in the expression of molecules in the JAK2/STAT3 signaling pathway between pancreatic cancer parental cells and radiotherapy-resistant cells, determined the impact of X-ray irradiation on this signaling pathway, and evaluated enhanced sensitivity to radiotherapy by the JAK2/STAT3 inhibitor, AG490, in pancreatic cancer cells. We show that JAK2 protein expression increased followed an increase in irradiation dose. Compared with parental cells, JAK2 and pSTAT3 were up-regulated in radiotherapy-resistant cells, whereas SOCS3 was down-regulated, X-ray irradiation can activate the JAK2/STAT3 signaling pathway; the combination of siJAK2 transfection with radiotherapy markedly increased cancer cell apoptosis, improving radiotherapy sensitivity of resistant pancreatic cancer cells;AG490, a JAK2-specific inhibitor, decreased radioresistance of pancreatic cancer cells by inhibiting the JAK2/STAT3 signaling pathway . In summary, inhibition of JAK2/STAT3 signaling pathway increases the sensitivity of radiotherapy-resistant pancreatic cancer cells in vitro.