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目的探讨化合物诱导的大鼠肺鳞癌癌变各阶段细胞周期调控蛋白P16、P27和P53水平动态变化趋势、相互关系及其在癌变过程中的作用。方法3-甲基胆蒽(MCA)及二乙基亚硝胺(DEN)碘油溶液诱发Wistar大鼠肺鳞癌。采用免疫组化S-P法检测P16、P27和P53蛋白在大鼠肺鳞癌癌变各阶段的表达水平,采用Westernblot检测鳞癌、癌旁和正常组织中各蛋白表达水平。结果共获取癌变各阶段标本164例,其中正常支气管上皮20例,增生25例,鳞状化生27例,不典型增生37例,原位癌30例,浸润癌25例。P16和P27蛋白表达的阳性率随癌变进展而降低,P53蛋白表达的阳性率随癌变进展而升高。P16与P27蛋白表达呈正相关(P<0.01),P16和P27蛋白表达与P53蛋白表达呈负相关(P<0.05)。鳞癌组织中P16与P27蛋白低表达,P53蛋白高表达,与正常组织或癌旁组织有显著性差异(P<0.01)。结论在癌变过程中细胞周期调控蛋白P16和P27表达下调,P53蛋白表达逐渐增强,可能与大鼠肺鳞癌的发生、发展密切相关。
OBJECTIVE: To investigate the dynamic changes of cell cycle regulatory proteins P16, P27 and P53 in various stages of carcinogenesis of lung squamous cell carcinomas induced by chemical compounds in rats and their roles in carcinogenesis. Methods Wistar rat lung squamous cell carcinoma was induced by 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN) iodine solution. Immunohistochemical S-P method was used to detect the expression of P16, P27 and P53 proteins in various stages of lung squamous cell carcinoma of the rat. Western blot was used to detect the expression of each protein in squamous cell carcinoma, adjacent normal tissues and normal tissues. Results A total of 164 specimens of all stages of cancer were obtained, of which 20 were normal bronchial epithelium, 25 hyperplasia, 27 squamous metaplasia, 37 atypical hyperplasia, 30 carcinoma in situ and 25 invasive carcinoma. The positive rate of P16 and P27 protein expression decreased with the progress of carcinogenesis. The positive rate of P53 protein expression increased with the progression of carcinogenesis. P16 and P27 protein expression was positively correlated (P <0.01), P16 and P27 protein expression and P53 protein expression was negatively correlated (P <0.05). The expression of P16 and P27 protein in squamous cell carcinoma was low, and P53 protein was highly expressed, which was significantly different from that in normal tissues or paracancerous tissues (P <0.01). Conclusions The expressions of P16 and P27 are down-regulated and P53 protein is gradually increased during carcinogenesis, which may be closely related to the occurrence and development of lung squamous cell carcinoma in rats.