Molecular analysis and application of differentiation induction therapy with intra-nuclear receptor and intra-cellular signal transduction factor

核内受体和细胞内信号转导因子分化诱导治疗的分子分析及应用

基本信息

批准号：
12470259
负责人：
SHIMADA Yutaka
金额：
$ 6.59万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470259/
关键词：
Intra-nuclear receptor PPARgamma RXR Intra-cellular signal transduction factor EGF STAT INFgamma 分化誘導療法

项目摘要

Interferon gamma as well as EGF inhibited the growth of esophageal cancer cells in 50% of the cell lines.STAT1 dominant negative cells demonstrated that this inhibitory effect was dependent on the STAT1. STATsignaling pathway was not harmful and induced Involculin in the normal esophageal squamous cell (NESC). In the KYSE70 cell which was not inhibited by EGF and INF gamma, hospholylation of the EGFR was not observed and the lack of INF gamma receptor was demonstrated. The growth of xeno-transplanted cells were inhibited by INF gamma and bioassay using explant culture was being checkedto predict INFgamma sensitivity.A specific ligand of PPARγ, troglitazone, led to G1 accumulation with the increase in p27 (Kip1), butnot p21 (Waf1/Cip1), and inhibited cellular proliferation in a pancreatic cancer cell line, Panc-1. The overexpression of PPARγ in a pancreatic cancer cell line, KMP-3, caused lipid accumulation, which suggested cell growth in some cancers might be inhibited, at least in par … More t, through terminal differentiation in the adipogenic lineage. In addition, implanted Panc-1 tumors in nude mice showed significant inhibition of tumor growth, when treated with pioglitazone, another specific ligand of PPARγ.RT-PCR andwestern blot analysis demonstrated that all ten tested human esophageal SCCcells, KYSE series, expressed PPAR gamma and RXR alfa. In luciferase assay, both troglitazone and pioglitazone transactivated the transcription of a peroxisome proliferator response element-driven promoter in a dose dependent fashion and when applied with 9-cis retinoic acid (9CRA), relative luciferase ctivity was elevated more strongly. Troglitazone inhibited growth of all ten tested cell lines where as pioglitazone inhibited 6 of these cell lines. In KYSE270 cells, cell cycle analysis by flow cytometry demonstrated that TZDs and 9CRA increased subG1 phase. Poly (ADP-ribose) polymerase (PARP) protein cleavage band was observed in the cells treated with TZDs and 9CRA. PARP cleavage band appeared at an early time point in the cells treated with both troglitazone and 9CRA, compared with pioglitazone and 9CRA simultaneously applied cells. P27 protein expression was increased to only the cells reated with both troglitazone and 9CRA. Simultaneous treatment of TZD and 9CRA is a promising therapeutic strategy of human esophageal squamous cell carcinoma. Less

干扰素伽玛和EGF抑制了50％的细胞系中食管癌细胞的生长。STAT1显性阴性细胞表明，这种抑制作用依赖于Statsignaling途径。（NESC）。 A，troglitazone，随着n p27的增加（KIP1），丁香p21（WAF1/CIP1）导致G1积累，并在胰腺癌细胞系中抑制细胞泛滥，PPAR -1的过表达。，在脂肪生成谱系中，至少在PAR中引起脂质积累，至少在PAR中均具有终端差异，此外，裸鼠小鼠的Imors显示出对肿瘤生长PPARγ.RT-PPAR的有些障碍。 kyse系列的食管Scccells在荧光素酶测定中表达PPARγ和RXR Alfa在所有测试线中，随着pioglitazone抑制这些细胞的6个。与pioglitazone和9cra相比，troglitazone 9c RA的细胞同时使用了troglitazone和9cra