Lentivirus-mediated shRNA interference targeting STAT3 inhibits human pancreatic cancer cell invasion

Abstract

AIM:To investigate RNA interference targeting signal transducer and activator of transcription-3 (STAT3) on invasion of human pancreatic cancer cells. METHODS:We constructed three plasmids of RNA interference targeting the STAT3 gene. After LV (lentivirus)-STAT3siRNA (STAT3 small interfering RNA) the vector was transfected into the human pancreatic cell line, SW1990 and cell proliferation was measured by the MTT assay. Flow cytometry was used to assess cell cycle. Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) mRNA and protein expression were examined by quantitative PCR and western blotting, respectively. The invasion ability of SW1990 cells was determined by cell invasion assay. RESULTS:We successfully constructed the LVSTAT3siRNA lentivirus vector and proved that it can suppress expression of STAT3 gene in SW1990 cells. RNA interference of STAT3 by the LV-STAT3siRNA construct significantly inhibited the growth of SW1990 cells, in addition to significantly decreasing both VEGF and MMP-2 mRNA and protein expression. Moreover, suppression of STAT3 by LV-STAT3siRNA decreased the invasion ability of SW1990 cells. CONCLUSION:The STAT3 signaling pathway may provide a novel therapeutic target for the treatment of pancreatic cancer since it inhibits the invasion ability of pancreatic cancer cells.

OSU-A9 inhibits pancreatic cancer cell lines by modulating p38-JAK-STAT3 signaling

“…In pancreatic cancer, down-regulation of STAT3 expression suppressed the growth and invasiveness of cancer cells, both in vitro and in vivo [27, 38]. In the present study, we observed that OSU-A9 significantly inhibited cell migration and invasiveness of BxPC-3 and PANC-1 cells (Figure 5).…”

MiR-130b Is a Prognostic Marker and Inhibits Cell Proliferation and Invasion in Pancreatic Cancer through Targeting STAT3

“…In pancreatic cancer, activation of STAT3 promoted tumor cell growth and invasion, which led to poor patient survival [22]. Furthermore, STAT3 knockdown inhibited the cell growth and invasiveness in pancreatic cancer both in vitro and in vivo , and markedly decreased VEGF and MMP-2 expressions [23], [24]. Therefore, the dual luciferase assay was applied to identify whether STAT3 was directly targeted by miR-130b.…”

Overexpression of STAT3 Potentiates Growth, Survival, and Radioresistance of Non-Small-Cell Lung Cancer (NSCLC) cells

“…Signal transducer and activator of transcription-3 protein (STAT3) is the most important member of the family of STAT, which has been reported to promote tumor proliferation, survival and angiogenesis by upregulating the expression of anti-apoptotic proteins (survivin, Bcl-xL and Mcl-1), cell cycle regulators (cyclin D1and c-Myc) and vascular endothelial growth factor (VEGF) [12][13][14][15]. STAT3 has been found to be highly up-regulated in many human cancers, such as breast cancer, renal cell carcinoma, bladder cancer, urothelial carcinoma, prostate cancer, and lung cancer [16][17][18][19][20][21].…”