MT-21 INHIBITS THE CELL GROWTH AND INVASIVENESS THROUGH AP-1 IN PANCREATIC CANCER CELL LINES

概要

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The prognosis of pancreatic cancer is very poor because of its potential for local invasion and early metastasis. It is necessary for improvement of the mortality of pancreatic cancer patients to look for new therapeutic modalities. MT-21, a novel adenine nucleotide translocation inhibitor, was shown to induce apoptosis in human leukemia cells. And also MT-21 was shown to activate INK which could activate the important transcriptional factor, AP-1. Therefore we examined the effect of MT-21 on pancreas cell growth and invasiveness, and the relationship between MT-21 and JNK/AP-1 pathway. On MTT assay, MT-21 inhibited growth of pancreatic cancer cell lines, BxPC-3, SW 1990, Capan-2 and MIA PaCa-2 in a dose-dependent manner. On invasion assay for Matrigel, MT-21 inhibited invasiveness of all four pancreatic cancer cells. In particular, 8 |iM of MT-21, which concentration had no effect on cell viability, inhibited invasiveness in BxPC-3 and SW 1990. On EMSA, MT-21 enhanced AP-l-DNA binding activity in a dose-dependent manner in SW 1990. We demonstrated that MT-21 inhibits cell growth and invasiveness through the JNK/AP-1 pathway in pancreatic cancer cells. MT-21 is a possible candidate as a therapeutic agent for pancreatic cancer.
名古屋市立大学の論文
2004-06-28