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目的:细胞凋亡受到抑制与大肠癌的发生有密切联系。近年来发现长期应用舒林酸等非甾体抗炎药(NSAID)对人的结肠癌、直肠癌和癌前病变的发生发展有预防作用。本实验试图通过对凋亡调控基因的观察,初步探讨舒林酸抗肿瘤作用可能存在的分子机制。方法:利用二甲肼诱发的小鼠实验性大肠癌动物模型,采用TUNEL原位杂交和免疫组化染色的方法,分别标记细胞凋亡、p53、p21阳性细胞,多阶段地动态观察诱癌过程中蛋白表达的变化和舒林酸对它们的影响。结果:p53蛋白表达阳性细胞密度随着病变加重而增加,p21阳性细胞密度升高趋势不明显,预防组、治疗组的p53和p21阳性率都与模型组无显著性差异(P>0.05)。预防组和治疗组中p53低于模型组(P<0.05),p21表达则高于模型组(P<0.05)。结论:舒林酸可以通过上调p21的表达,抑制突变型p53的表达,诱导细胞凋亡,抑制肿瘤形成和进展。
Objective: Inhibition of apoptosis is closely related to the occurrence of colorectal cancer. In recent years, found that long-term use of sulindac and other non-steroidal anti-inflammatory drugs (NSAID) on human colon cancer, rectal cancer and precancerous lesions have a preventive effect. This experiment attempts to investigate the molecular mechanism of the anti-tumor effect of sulindac through the observation of apoptosis-controlling genes. Methods: The mouse model of experimental colorectal cancer induced by dimethylhydrazine was established. TUNEL in situ hybridization and immunohistochemistry were used to detect the apoptosis and p53, p21 positive cells respectively. Changes in protein expression and the effects of sulindac on them. Results: The positive rate of p53 protein positive cells increased with the increase of pathological changes, while the positive rate of p21 positive cells was not obvious. The positive rates of p53 and p21 in the prevention group and the treatment group were not significantly different from those in the model group (P> 0.05). The levels of p53 in the prevention group and the treatment group were lower than those in the model group (P <0.05), while those in the model group were higher than those in the model group (P <0.05). Conclusion: Sulindac can inhibit the expression of p21, suppress the expression of mutant p53, induce apoptosis and inhibit tumor formation and progression.