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

放疗、化疗和热疗是治疗头颈部肿瘤的有效方法。我们使用了两种不同功能背景的人鳞状细胞癌(SAS)细胞系，即带有mp53蛋白的SAS/mp53细胞和带有wtp53的SAS/neo细胞。我们先前报道，与SAS/mp53细胞相比，SAS/neo细胞的热敏感性和凋亡率明显较高。为了阐明热处理后细胞凋亡相关蛋白的表达情况，我们利用蛋白质芯片技术进行了分析。热处理可使表达mP53的SAS细胞中的凋亡抑制蛋白Bcl2、Bclxl、NF-кB、COX2、STAT3、IL6和IKKα/1的表达增加，而在表达wtP53的SAS细胞中表达不明显。提示这些蛋白可抑制mP53细胞热诱导的细胞凋亡。这些发现强烈表明，P53状态是一个有用的候选指标，可以预测热疗的有效性。放射治疗口腔鳞癌的疗效和提高晚期患者生存率的能力有限。在照射携带突变型p53(Mp53)基因的口腔鳞癌细胞系(Ca9-22)之前，在培养液中加入甘油可以增加这些细胞的放射敏感性。当甘油存在于培养液中时，虽然X射线或甘油本身都不能增加细胞的凋亡程度，但在X射线照射后，甘油增加了Ca9-22细胞的辐射敏感性和凋亡程度。这些发现表明，甘油的预治疗可能会增强携带mp53基因突变的口腔鳞癌的放射治疗效果。

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.