[Stem cell factor enhances invasive ability of BxPC-3 cells via hypoxia-inducible factor 1α (HIF-1α)]

Objective To investigate the effect of stem cell factor (SCF)/c-KIT system on the invasion of BxPC-3 pancreatic cancer cells and the role of hypoxia-inducible factor 1 alpha (HIF-1α) in this effect. Methods BxPC-3 cells were cultured in normoxia and hypoxia. The cells cultured in normoxia were treated with SCF. Real-time quantitative PCR and Western blotting were used to investigate the expressions of HIF-1α mRNA and protein, respectively. Small interference RNA of HIF-1α (siHIF-1α) was designed and synthesized, and then transfected into BxPC-3 cells. The expressions of matrix metalloproteinase-2 (MMP2), MMP9, and urokinase type plasminogen activator (uPA) were detected by real-time quantitative PCR and Western blotting in BxPC-3 cells after treated with SCF or siHIF-1α. The effects of SCF/c-KIT and HIF-1α knockdown on BxPC-3 cell invasion were examined by Transwell^TM assay. Results Either SCF or hypoxia could induce the protein expression of HIF-1α. The siHIF-1α down-regulated the expression of HIF-1α specifically in BxPC-3 cells. SCF up-regulated the mRNA and protein expressions of MMP2, MMP9 and uPA, while siHIF-1α down-regulated the expressions of these genes. The invasive ability of BxPC-3 cells were enhanced by SCF, while siHIF-1α played an opposite role. Conclusion SCF/c-KIT system up-regulates the mRNA and protein expressions of MMP2, MMP9 and uPA through HIF-1α, which enhances the invasive ability of pancreatic cancer cells. And siHIF-1α can effectively inhibit these effects.