Figure 6. Hypothetical model.

ROS, autophagy and inflammation play critical roles in PanCA progression. ROS is known to activate inflammatory transcription factor STAT3. Our data indicates that (i) STAT3 regulates autophagy possibly by transcriptional regulation of LC3; and (ii) treatment with Nx inhibits autophagy and reduces ROS generation. Further, pharmacological inhibition of ROS inhibits autophagy while pharmacological or genetic inhibition of autophagy inhibits ROS suggesting a positive feedback. Our working model is that Nx inhibits pancreatic cancer cell growth by interrupting the positive feedback loop between autophagy, ROS and STAT3. Nx mediated inhibition is indicated by downward arrow.