The basic and clinical study for the personalized oral cancer therapy

口腔癌个性化治疗的基础与临床研究

基本信息

批准号：
19390523
负责人：
FUKUDA Masakatsu
金额：
$ 10.73万
依托单位：
Meikai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2009
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390523/
关键词：
頭頸部悪性腫瘍遺伝子変異 NF-κB p53 ING アポトーシス NF-кB

项目摘要

Human oral squamous cell carcinoma (HOSCC) is the most common malignant tumor in the oral cavity, and that frequent alteration of p53 tumor suppressor gene is associated with the development of HOSCC, especially in 30% to 50% of that. The p33^<ING1b> has a close relationship with p53 and that neither p53 nor p33^<ING1b> alone can cause cell growth inhibition, which prompted us to investigate their potential role in oral carcinogenesis. Furthermore, Nuclear factor-κB (NF-κB) has key roles in inflammation, immune response, tumorigenesis and protection against apoptosis. It has recently been reported that the function of NF-κB is regulated by p53. In this study, to determine whether the p33^<ING1b> isoform plays a role in chemosentivity of HOSCC, we investigated the effect of p33^<ING1b> overexpression on taxol-induced apoptosis and the activation of caspases in HOSCC cells. Previous experimental evidences indicated that p33^<ING1b> functionally cooperates with p53 in controlling cell growth, senescence and apoptosis. The p33^<ING1b> may cooperate with p53 in taxol-induced apoptosis of the HOSCC. To test this hypothesis, the HOSCC cell lines, contained wild-type p53 and mutant p53, were employed to examine the enhancement ofapoptosis by p33^<ING1b> overexpression and its mechanism. We found that overexpression of exogenous p33^<ING1b> in wild-type p53 cell line can dramatically promote taxol-induced apoptosis.

人类口腔鳞状细胞癌(HOSCC)是口腔最常见的恶性肿瘤，p53抑癌基因的频繁改变与HOSCC的发生有关，尤其是30%～50%的p33^<。 ING1b>与p53有密切的关系，p53和p33^<ING1b>单独都不能引起细胞生长抑制，这促使我们研究它们在口腔癌发生中的潜在作用。此外，核因子-κB (NF-κB) 在炎症、免疫反应、肿瘤发生和细胞凋亡保护中发挥着关键作用，最近有报道称 NF-κB 的功能受到 p53 的调节。 p33^<ING1b>亚型在 HOSCC 的化学敏感性中发挥作用，我们研究了 p33^<ING1b> 过表达对紫杉醇诱导的细胞凋亡和半胱天冬酶激活的影响HOSCC 细胞。先前的实验证据表明，p33^<ING1b> 在控制细胞生长、衰老和凋亡方面与 p53 协同作用。为了验证这一假设，p33^<ING1b> 可能与 p53 协同作用。采用含有野生型 p53 和突变型 p53 的 HOSCC 细胞系来检测 p33^<ING1b> 过表达及其对细胞凋亡的增强作用。我们发现野生型p53细胞系中外源p33^<ING1b>的过度表达可以显着促进紫杉醇诱导的细胞凋亡。