Expression of KLF9 in pancreatic cancer and its effects on the invasion, migration, apoptosis, cell cycle distribution, and proliferation of pancreatic cancer cell lines

Abstract

Kruppel-like factor 9 (KLF9), a transcription factor, is critical for the inhibition of growth and development of tumors, whereas its effects in pancreatic cancer remains unclear. The purpose of the present study was to investigate the expression and functional significance of KLF9 invitro, by assessing the expression of KLF9 in pancreatic cancer tissue samples and its association with the total survival of patients and clinicopathological data. The levels of KLF9 expression in adjacent tissues and pancreatic cancer tissues were detected using immunohistochemistry. Using western blot analyses, we assessed KLF9 expression in human pancreatic cancer cell lines. Using flow cytometric analysis and CCK-8, we evaluated the effects of KLF9 expression on cell apoptosis, the cell cycle and proliferation of pancreatic cancer cells. Its effects on migration and cell invasion were detected by performing Transwell assay. By conducting western blot analyses, we evaluated the expression of relative target proteins (involved in invasion, migration, apoptosis, and cell cycle distribution. Our results revealed that in both tissue samples and cell lines (particularly in BxPC-3 and PANC-1 cells) of pancreatic cancer, KLF9 exhibited relatively lower expression. In addition, low KLF9 expression was related to the differentiation (P<0.001) and depth of vascular invasion (P=0.016) and was associated with a poor overall survival rate. In PANC-1 and BxPC-3 cells, KLF9 overexpression decreased the proliferation of pancreatic cancer cells, induced apoptosis, blocked the cell cycle at the Sphase, and inhibited the migration and invasion of tumor cells. KLF9 overexpression downregulated MMP-9, MMP-2 Bcl-2, N-cadherin and cyclinB, and upregulated the levels of E-cadherin, Bax, p53, CDK4 and cyclin D1. On the whole, our findings indicated that KLF9 exhibited low expression in pancreatic cancer, and upregulation of KLF9 may inhibit the progression of pancreatic cancer. KLF9 may have potential diagnostic and therapeutic values in this type of cancer.