当前位置： SCI文献检索 > PANCREAS期刊下所有文献 > Endogenous tumor necrosis factor inhibits the cytotoxicity of exogenous tumor necrosis factor and adriamycin in pancreatic carcinoma cells.

Endogenous tumor necrosis factor inhibits the cytotoxicity of exogenous tumor necrosis factor and adriamycin in pancreatic carcinoma cells.

Abstract：

:Pancreatic carcinoma is one of the most devastating neoplasms with regard to its resistance to conventional therapy. In a previous report, we found that endogenous tumor necrosis factor (enTNF) exerts an intracellular protective effect against exogenous TNF- and Adriamycin (ADM)-induced cytotoxicity by scavenging oxygen free radicals (OFR) with induced manganous superoxide dismutase (MnSOD). We also know that glutathione S-transferase pi (GST-pi) and glutathione (GSH) also scavenge OFR. It remains unclear to what extent enTNF and MnSOD induced by enTNF regulate the sensitivity to ADM and exogenous TNF among different carcinoma cells. In this study, we examined the relationship between ADM and exogenous TNF sensitivity and en-TNF expression and MnSOD activity in four pancreatic carcinoma lines. We determined whether ADM and exogenous TNF sensitivity could be predicted by measuring enTNF expression and MnSOD activity in the carcinoma cells. The sensitivity to TNF and ADM varied with the cell lines, and TNF sensitivity correlated well with Adriamycin sensitivity. Moreover, enTNF expression and Mn-SOD activity correlated positively with resistance to ADM and exogenous TNF. When MIAPaCa-2 cells, which had the lowest enTNF expression and the highest sensitivity to exogenous TNF and ADM, were transfected with the nonsecretory-type human TNF gene (pTNF delta pro) to increase enTNF synthesis, their intracellular MnSOD activity and exogenous TNF and ADM resistance were increased. These findings suggest that MnSOD plays a critical role in scavenging OFR induced by ADM and exogenous TNF. enTNF is the most important factor that regulates the production of MnSOD. Therefore, it is plausible that inhibition of enTNF expression or MnSOD activity in pancreatic carcinoma would improve the efficacy of therapies for pancreatic carcinoma.

journal_name

Pancreas

journal_title

Pancreas

authors

Watanabe N,Tsuji N,Tsuji Y,Sasaki H,Okamoto T,Akiyama S,Kobayashi D,Sato T,Yamauchi N,Niitsu Y

doi

10.1097/00006676-199611000-00009

subject

Has Abstract

pub_date

1996-11-01 00:00:00

pages

395-400

issue

eissn

0885-3177

issn

1536-4828

journal_volume

pub_type

杂志文章

在线工具

Endogenous tumor necrosis factor inhibits the cytotoxicity of exogenous tumor necrosis factor and adriamycin in pancreatic carcinoma cells.