Apoptosis-related gene expression after irradiation, chemotherapy and hyperthermia in Oral cancer

头颈部恶性肿瘤的放疗、化疗和热疗是目前治疗头颈部恶性肿瘤的有效方法，本研究采用两种除p53蛋白表达外，其他功能背景完全相同的人鳞状细胞癌（SAS）细胞系，即含mp53的SAS/mp53细胞系和含wtp 53的SAS/neo细胞系。我们以前报道过SAS/neo细胞的热敏感性和凋亡频率明显高于SAS/mp53细胞。为了阐明热处理后凋亡相关蛋白的表达，我们使用蛋白质微阵列分析。热处理可增加表达mp53的SAS细胞中Bcl-2、Bcl-xL、NF-кB、COX 2、Stat 3、IL 6和IKKα/1等凋亡抑制蛋白的表达，但对表达wtp 53的SAS细胞无影响。这表明，热诱导的细胞凋亡抑制这些蛋白质在mp53细胞。这些研究结果强烈暗示p53状态是一个有用的候选人的一个预测指标，在热疗的有效性。放射治疗口腔鳞状细胞癌是有限的，在其有效性和提高生存率的能力，在一个先进的阶段。甘油的添加到培养基中的照射前的口腔鳞状细胞癌细胞系（Ca 9 -22）携带突变型p53（mp53）基因被发现增加这些细胞的放射敏感性。甘油，当存在于培养基中，增强辐射敏感性和细胞凋亡的程度后，X射线照射在Ca 9 -22细胞，虽然既不X射线或甘油单独增加细胞凋亡的程度。这些研究结果表明，甘油预处理可能会提高放射治疗对口腔鳞状细胞癌携带mp53基因突变的有效性。

Irradiation, chemotherapy and hyperthermia is useful for the treatment of human head and neck cancer.We used two kinds of cell lines of a human squamous cell carcinoma (SAS) with identical backgrounds of function except for the p53 protein, which are SAS/mp53 cells with mp53 and SAS/neo cells with wtp53. We previously reported that the heat sensitivity and frequency of apoptosis in SAS/neo cells were clearly high as compared with SAS/mp53 cells. In order to elucidate the expression of apoptosis-related proteins after heat treatment, we used protein microarray analysis. The expression of apoptosis-inhibitive proteins, such as Bcl-2, Bcl-xL, NF-кB, COX2,Stat3, IL6 and IKKα/1, were increased by heat treatment in SAS cells expressing mp53, but not in SAS cells with wtp53. It is suggested that heat-induced apoptosis was suppressed by these proteins in the mp53 cells. These findings strongly imply that p53 status is a useful candidate for a predictive indicator of the effectiveness in hyperthermic therapy.Radiotherapy for oral squamous cell carcinomas is limited in its efficacy and in its ability to improve the survival rate in patients with an advanced stage. The addition of glycerol to the culture medium prior to irradiation of an oral squamous cell carcinoma cell line (Ca9-22) bearing a mutant p53 (mp53) gene was found to increase the radiosensitivity of these cells. Glycerol, when present in the culture medium, enhanced the radiation sensitivity and extent of apoptosis following X-irradiation in the Ca9-22 cells, although neither X-rays or glycerol alone increased the extent of apoptosis. These findings suggest that pre-treatment with glycerol may enhance the effectiveness of radiotherapy against oral squamous cell carcinomas bearing an mp53 gene mutation.