Vairaktaris E, Kalokerinos G, Goutzanis L, Yapijakis C, Derka S, Vassiliou S, Spyridonidou S, Vylliotis A, Nkenke E, Lazaris A, Patsouris E
Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Vas. Sofias 93 & Dim. Soutsou 1, Athens 11521, Greece.
Int J Oral Maxillofac Surg. 2008 Jan;37(1):60-5. doi: 10.1016/j.ijom.2007.06.012. Epub 2007 Sep 6.
Markers of cell proliferation (Ki-67 antigen) and apoptosis (Bax, Bcl-2) were studied in an experimental model of chemically induced carcinogenesis in normal and diabetic (type I) Sprague-Dawley rats. Thirteen diabetic and 12 normal rats developed cancer after 4-nitroquinoline-N-oxide treatment, while 6 diabetic and 6 normal animals were used as controls. The biopsies were classified pathologically (from oral mucosal dysplasia to moderately differentiated squamous cell carcinoma) and studied immunohistochemically using monoclonal antibodies against Bax, Bcl-2 and Ki-67 proteins. The Bcl-2/Bax ratio was almost stable during the oncogenesis process in the diabetic rats, whereas the normal rats showed an increased Bcl-2/Bax ratio during the stage of moderately differentiated carcinoma. In contrast, Ki-67 expression was higher in diabetic rats than in normal ones in almost all stages of oral oncogenesis, and it reached significantly increased levels in the stages of normal control tissue, dysplasia and moderately differentiated squamous cell carcinoma. These data suggest that diabetes results in increased cell proliferation during oral oncogenesis, but this is accomplished without affecting the Bax/Bcl-2-mediated apoptotic pathways.
在正常和糖尿病（I型）斯普拉格-道利大鼠化学诱导致癌的实验模型中，研究了细胞增殖标志物（Ki-67抗原）和细胞凋亡标志物（Bax、Bcl-2）。13只糖尿病大鼠和12只正常大鼠在经4-硝基喹啉-N-氧化物处理后发生了癌症，而6只糖尿病动物和6只正常动物用作对照。对活检组织进行病理分类（从口腔黏膜发育异常到中度分化的鳞状细胞癌），并使用针对Bax、Bcl-2和Ki-67蛋白的单克隆抗体进行免疫组织化学研究。在糖尿病大鼠的肿瘤发生过程中，Bcl-2/Bax比值几乎稳定，而正常大鼠在中度分化癌阶段Bcl-2/Bax比值升高。相反，在口腔肿瘤发生的几乎所有阶段，糖尿病大鼠的Ki-67表达均高于正常大鼠，且在正常对照组织、发育异常和中度分化鳞状细胞癌阶段显著升高。这些数据表明，糖尿病导致口腔肿瘤发生过程中细胞增殖增加，但这一过程并未影响Bax/Bcl-2介导的细胞凋亡途径。
