The basic and clinical study for the personalized oral cancer therapy

口腔鳞状细胞癌是口腔最常见的恶性肿瘤，P53抑癌基因的频繁改变与口腔鳞状细胞癌的发生发展密切相关，尤其是30%~50%的口腔鳞状细胞癌。P33^lt；ING1b&gt；与P53的关系密切，P53和p33^lt；ING1b&gt；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、肿瘤发生和抗细胞凋亡等方面发挥着重要作用。最近有报道称，NF-κB的功能受P53的调节。在本研究中，我们研究了p33^&lt；ING1b&gt；过表达对紫杉醇诱导的HOSCC细胞凋亡和caspase激活的影响，以确定p33^&lt；ING1b&gt；异构体是否在HOSCC的化疗敏感性中起作用。以往的实验证据表明，p33^&lt；ING1b&gt；在控制细胞生长、衰老和凋亡方面与p53在功能上具有协同作用。在紫杉醇诱导的HOSCC细胞凋亡中，p33^lt；ING1b&gt；可能与P53协同作用。为了验证这一假说，我们利用含有野生型和突变型P53的HOSCC细胞株，研究了p33^&lt；ING1b&gt；过表达对细胞凋亡的促进作用及其机制。我们发现外源p33^&lt；ING1b&gt；在野生型p53细胞中的过表达可以显著促进紫杉醇诱导的细胞凋亡。

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.