目的:探讨口腔鳞癌中ToPoⅡα的表达水平与临床PTP方案(顺铂+替尼泊甙+平阳霉素/博莱霉素)化疗效果之间的相关性,初步评价其表达水平是否可以指导临床PTP的应用。方法:采用回顾性研究的方法检测了46例原发口腔鳞癌标本化疗前ToPoⅡα与p53表达情况.评价其与临床化疗效果的相关性:对比分析其中18例标本化疗前后ToPoⅡα的表达变化。同时,采用Western印迹法分析8种口腔鳞癌细胞系内TOP01/仅表达水平与化疗药物替尼泊甙的半数抑制浓度之间的关系。结果:46例口腔鳞癌患者中ToPoⅡα均有不同程度的表达,其表达水平与化疗疗效呈显著正相关;体外实验也证实8种细胞系中ToPoⅡα的表达水平与口腔鳞癌细胞系对替尼泊甙的敏感性显著相关。与化疗前相比,化疗后口腔鳞癌标本中ToPoⅡα的表达明显下降,提示有继发性耐药产生的可能性。p53的表达水平与化疗疗效无显著相关性,也与ToPoⅡα的表达水平没有相关性。结论:实验结果表明,ToPoⅡα的表达水平能够指导临床应用PTP化疗方案治疗口腔鳞癌,而p53的表达水平对临床化疗效果提示作用不明显。
Objective: To evaluate the correlations between topoisomerase Ⅱ alpha (ToPoⅡα) expression and clinical treatment effects of PTP (cisplatin+teniposide+peplomycin/bleomycin) on oral squamous cell carcinoma (OSCC) patients. Methods: The expression levels of ToPoⅡαand p53 in 46 cases of OSCC before chemotherapy were examined immunohistochemically, in which, 18 cases were examined before and after chemotherapy. The correlation between expression level and clinical effects of PTP based chemotherapy was tested. The expression of ToPoⅡα in eight OSCC cell lines was further examined by Western blotting to investigate the correlation of ToPoⅡα expression and IC50 of teniposide in vitro. Results: Expression of ToPoⅡα was detected in all cases. There was a significant correlation between ToPoⅡα expression and chemotherapeutic effect. In vitro studies on the eight OSCC cell lines further confirmed this observation. The ToPoⅡαexpression level markedly declined after chemotherapy, which might indicate an acquired drug resistance. No correlation had been observed between the expression level of p53 and chemotherapeutic effect in these 46 OSCC cases. Conclusion: ToPoⅡα expression level is useful to predict the clinic effects of PTP based chemotherapy in OSCC patients.