To study the effect and mechanisms of TW-37 on cell proliferation, apoptosis, invasion and angiogenesis in pancreatic cancer cells in vitro and further explore the potential mechanism.

BxPC3 and HPAC cells were pretreated with TW-37 using untransfected or transfected with NF-κB p65 cDNA(p65 cDNA)or NF-κB p65 siRNA(siRNA-p65)cells as controls. Cell viability was determined by MTT assay. Cell apoptosis was assessed by enzyme-linked immunosorbent assay (ELISA). Cell invasion and angiogenesis was detected by Transwell and endothelial tube formation assay of HUVECs. ELISA assay was used to measure the activity of NF-κB, and its target proteins of MMP-9 and VEGF were detected by western blot.

TW-37 suppressed cell growth and induced apoptosis (A405: 1.29±0.21 vs 0.09±0.01, 1.07±0.18 vs 0.08±0.01), inhibited NF-κB activity and protein expression of NF-κB p65, VEGF and MMP-9(all P<0.05)in a dose- and time-dependent manner. The number of cells that invaded across the matrigel in the transwell chamber was (46.7±5.24) and (10.3±1.26)/×200 in BxPC3 control and 0.75 μmol/L TW-37 group (P=0.001). The number of tube formation was (39.4±4.36) and (7.84±1.25)/×200, (P=0.001). NF-κB activity was increased by p65 cDNA transfection, and decreased by TW-37 treatment in both of the two cell lines (P<0.05). However, NF-κB activity was decreased by p65 siRNA transfection, and greatly decreased by TW-37 treatment in both two cell lines (P<0.05 or P<0.01). Transfection of p65 cDNA did not significantly affect cell apoptosis. Transfection of p65 siRNA increased cell apoptosis, and greatly increased by TW-37 treatment in both two cell lines (all P<0.01).

TW-37 could inhibit the proliferation, invasion and angiogenesis in pancreatic cancer cells by regulating NF-κB signal pathway.

Pancreatic neoplasms; Growth; Neoplasm metastasis; Neovascularization, pathologic; TW-37