Objectives: Pancreatic cancer is a highly chemoresistant tumor and underlying mechanisms are not well understood. Sex determining region Y box 9 (Sox9) is a transcription factor playing important roles on maintenance of pluripotent cells during pancreatic organogenesis. The purpose of this study is to evaluate the roles of Sox9 in pancreatic cancer.
Methods: The Sox9 expression was evaluated by immunohistochemical analysis. Effects of Sox9 inhibition by siRNA or shRNA on chemosensitivity, sphere formation, stem cell markers expression, and in vivo tumor formation rate were examined using pancreatic cancer cell lines.
Results: High expression of Sox9 in pancreatic cancer tissue is correlated with poor prognosis (P = 0.011). Cells with high Sox9 expression (PANC-1, Capan-1) showed stronger chemoresistance to Gemcitabine than cells with low Sox9 expression (BxPC-3, MIA PaCa-2). The chemosensitivity in PANC-1 was recovered by suppressing Sox9 using siRNA (P < 0.05). Both sphere formation rate and the proportion of CD44CD24 cells were decreased by Sox9 inhibition. Tumor formation rate of Tet-on inducible Sox9 shRNA-transfected PANC-1 cells in KSN/Slc nude mice was decreased by induction of shRNA with doxycycline feeding (P < 0.05).
Conclusion: Sox9 plays an important role in chemoresistance by the induction of stemness in pancreatic cancer cells.