Gastrin suppresses growth of CCK2 receptor expressing colon cancer cells by inducing apoptosis in vitro and in vivo.

Background & Aims: The role of amidated gastrin17 (G17) and the gastrin/CCKB/CCK2 receptor in colorectal carcinogenesis is still a controversial issue. Here, we investigated the effect of G17 on proliferation and apoptosis of CCK2 receptor-expressing human colon cancer cell lines in vitro and in vivo.

Methods: Proliferation was determined by cell counting and cell cycle analysis.

Increased expression of the E3-ubiquitin ligase receptor subunit betaTRCP1 relates to constitutive nuclear factor-kappaB activation and chemoresistance in pancreatic carcinoma cells.

The permanent activation of the transcription factor nuclear factor-kappaB (NF-kappaB) in pancreatic cancer cells is associated with a profound resistance towards chemotherapy. In the present study, we show that chemoresistant pancreatic cancer cell lines exhibiting constitutive NF-kappaB activity (i.e.

[Autocrine IL-1beta secretion leads to NF-kappabeta-mediated chemoresistance in pancreatic carcinoma cells in vivo].

Background And Purpose: The pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly malignant phenotype and a profound chemoresistance. Thus, options for an effective treatment of this disease are still quite poor. In this study, it was investigated whether the autocrine secretion of interleukin-(IL-)1beta is related to a chemoresistant phenotype of PDAC cells in vivo.

Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma cells involving increased secretion and paracrine effects of nitric oxide and interleukin-1beta.

Pancreatic ductal carcinoma is characterized by a profound chemoresistance. As we have shown previously, these tumor cells can develop chemoresistance by interleukin (IL)-1beta in an autocrine and nuclear factor-kappaB-dependent fashion. Because pancreatic ductal carcinoma contains many mesenchymal stromal cells, we further investigated how tumor-stroma interactions contribute to chemoresistance by using a transwell coculture model, including murine pancreatic fibroblasts and the chemosensitive human pancreatic carcinoma cell lines T3M4 and PT45-P1.

Usage of the NF-kappaB inhibitor sulfasalazine as sensitizing agent in combined chemotherapy of pancreatic cancer.

Sulfasalazine is commonly used as an anti inflammatory agent and is known as a potent inhibitor of NF-kappaB. Some pancreatic carcinomas are characterized by a constitutively elevated NF-kappaB activity accounting for chemoresistance. To elucidate whether blockade of NF-kappaB activity with sulfasalazine is suitable for overcoming this chemoresistance in vivo, we employed a mouse model with subcutaneously xenotransplanted human Capan-1 pancreatic carcinoma cells.