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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，尤其是在30%~50%的HOSCC中。p33 ^与p53有着密切的关系，而p53和p33 ^均不能单独引起细胞生长抑制，这促使我们研究它们在口腔癌发生中的潜在作用。<ING1b><ING1b>此外，核因子-κ B（NF-κ B）在炎症、免疫反应、肿瘤发生和抗凋亡中起着关键作用。最近有报道NF-κ B的功能受p53的调节。在本研究中，为了确定p33 β亚型是否在卵巢癌的化疗敏感性中起作用，我们研究了p33 β过表达对紫杉醇诱导的卵巢癌细胞凋亡和半胱天冬酶激活的影响。<ING1b><ING1b>已有的实验证据表明，p33在调控细胞生长、衰老和凋亡方面与p53有协同作用。<ING1b>p33~+和p53~+可能在紫杉醇诱导的卵巢癌细胞凋亡中起协同作用。<ING1b>为了验证这一假设，我们采用了含有野生型p53和突变型p53的HOSCC细胞系来研究p53过表达对三聚体的增强作用及其机制。<ING1b>我们发现，外源性p33~+在野生型p53细胞系中过表达可显著促进紫杉醇诱导的细胞凋亡。<ING1b>