In conclusion, our data indicated that Rab14 was overexpressed in pancreatic cancer and promotes growth and gemcitabine resistance, possibly through regulation of mitochondrial function and Bcl-2.
The expression of anti-apoptotic Bcl-2 was downregulated and that of the pro-apoptotic Bax and cleaved caspase-3 was upregulated in AEG-1-silenced pancreatic cancer cells.
Herein, we investigated a therapeutic approach involving delivery of a short interfering double-stranded RNA (dsRNA), specific to Bcl2, with 5' triphosphate ends, by lipid calcium phosphate nanoparticles, in an orthotopic allograft KPC model of pancreatic cancer.
IFN-γ treatment decreased the expression and secretion of CXCL8 in BxPC-3 PC cells, suppressed the proliferation and migration of these cells, and enhanced their apoptosis, as determined by increased levels of cleaved Caspase-8 and Bax together with reduced expression of Bcl-2.
The synergistic effect of gemcitabine combined with specific B cell CLL/lymphoma 2 (Bcl-2) inhibitor ABT-199 against pancreatic cancer was tested using cell viability, cell cycle, and apoptosis assays in vitro and in an MIA Paca-2 xenograft model in vivo.
These results indicate that Bcl-xL is responsible for TRAIL resistance in human pancreatic cancer cells, and that Bcl-2 family inhibitors could represent promising reagents to sensitize human pancreatic cancers in DR-targeting therapy.
MM41 is a quadruplex-interactive compound which binds strongly to the quadruplexes encoded in the promoter sequences of the BCL-2 and k-RAS genes, both of which are dis-regulated in many human pancreatic cancers.
The expression of anti-apoptosis gene Bcl-2 associated anthanogen-1 (Bag-1), has been associated with outcome in several cancer types, however its prognostic role in pancreatic cancer is unknown.
The siRNA-mediated knockdown of bcl-2 leads to pronounced anti-tumor effects in a pancreatic cancer model, especially in combination with chemotherapy even at otherwise ineffective concentrations.
Aspirin inhibits GSK-3beta activation and suppresses the expression of its downstream gene products (cyclin D1 and Bcl-2), which are implicated in proliferation, survival and chemoresistance of pancreatic cancer.
On the other hand, the induction of autophagy by the inhibition of anti-autophagic proteins, such as Bcl-2, PKCdelta, and tissue transglutaminase 2 (TG2), may lead to autophagic cell death in some apoptosis-resistant cancers (i.e., breast and pancreatic cancers), indicating that the induction of autophagy alone may also be used as a potential therapy.
Resveratrol inhibited the proliferation of 4 different human PaCa cell lines, synergized the apoptotic effects of gemcitabine, inhibited the constitutive activation of NF-kappaB and expression of bcl-2, bcl-xL, COX-2, cyclin D1 MMP-9 and VEGF.
We have previously reported that TW-37, a small-molecule inhibitor of Bcl-2 family proteins, inhibited cell growth and induced apoptosis in pancreatic cancer.