A study on the senescence-inducing therapy to oral cancer by targeting IκB kinase

目的探讨IκB激酶（IKK）α在口腔鳞状细胞癌（SCC）中的作用。(1)本研究首先检测IKK和NF-κB在口腔鳞癌组织中的表达。IKK α是激活NF-κB的激酶，NF-κB是反式激活抗凋亡基因的转录因子。对36例SCC患者的活检标本进行了化学染色。结果表明IKKα和NF-κB p65的高表达与口腔鳞癌的侵袭性和淋巴结转移密切相关。(2)我们通过转染IKKα或IKKβ表达载体，使体外培养的口腔鳞癌细胞系过表达IKKα或IKKβ。高水平的IKKα而非IKKβ可抑制SCC细胞中上皮分化标志物外皮蛋白和丝聚蛋白的表达。肉豆蔻酸佛波酯可磷酸化IKKα，抑制外皮蛋白的表达。蛋白激酶C和IKKα对SCC细胞的分化和衰老有调节作用，提示IKKα高表达可能通过抑制SCC细胞的分化（和衰老）而促进肿瘤的存活。因此，IKKα可能是口腔癌治疗的靶分子。

We investigated the function of IκB kinase (IKK) α in oral squamous cell carcinoma (SCC).(1) At first, we examined the expressions of IKK as well as NF-κB in oral SCC tissues. IKK α is a kinase to activate NF-κB, and NF-κB is a transcription factor to transactivate anti-apoptotic genes. Thirty six biopsy specimens from patients with SCC were immunohistochemically stained. The results show that high expressions of IKKα and NF-κB p65 correlated with the invasiveness and the nodal involvement of oral SCC.(2) We caused cultured oral SCC cell line to overexpress IKKα or IKKβ by transfecting its expression vector. High levels of IKKα, but not IKKβ, inhibited the expressions of epithelial differentiation markers, involucrin and filaggrin, in SCC cells. Phorbol myristate acetate phosphorylated IKKα to inhibit the expressions of involucrin. Protein kinase C and IKKα may regulate the differentiation and senescence of SCC cells.The results described above suggest that high expressions of IKKα may contribute to the tumor survival by inhibiting the differentiation (and senescence) in SCC cells. Therefore, IKKα seems to be a therapeutic target molecule against oral cancer.