论文部分内容阅读
目的探讨选择性环氧化酶-2(COX-2)抑制剂尼美舒利(NIM)对二甲基苯并蒽(DMBA)诱导的大鼠乳腺癌的影响及其作用机制。方法将76只大鼠随机分为致癌组(30只)、NIM组(30只)、饮食对照组(8只)及NIM药物对照组(8只),观察乳腺肿瘤诱发率。通过逆转录聚合酶链反应方法、蛋白印迹法测定每组肿瘤组织中COX-2mRNA含量及其蛋白表达水平;放射免疫法测定各组大鼠血浆、肿瘤组织中前列腺素E2(PGE2)含量;TUNEL法、增殖细胞核抗原分别检测凋亡和增殖指数。结果NIM组(40.3%)大鼠乳腺肿瘤发生率明显低于致癌组(69.2%);NIM组COX-2mRNA、蛋白水平较致癌组明显下调[A值:(0.21±0.05)vs.(0.46±0.12),P<0.05;(30.26±8.75)vs.(58.13±10.02),P<0.05],血浆、肿瘤组织中PGE2的含量显著降低[(233±59)pg/mlvs.(452±82)pg/ml,P<0.01;(167±42)pg/mg蛋白vs.(250±67)pg/mg蛋白,P<0.05];NIM组肿瘤细胞的增殖指数与致癌组相比下降[(20±5)vs.(36±5),P<0.01],凋亡指数明显增高[(43±13)vs.(18±7),P<0.01],差异有统计学意义。结论NIM通过下调COX-2的表达,抑制前列腺素的合成,抑制肿瘤细胞的增殖、诱导凋亡,降低DMBA诱发大鼠乳腺癌的发生率。
Objective To investigate the effect of nimesulide (NIM), a selective cyclooxygenase-2 (COX-2) inhibitor, on rat breast cancer induced by dimethylbenzanthracene (DMBA) and its possible mechanism. Methods Totally 76 rats were randomly divided into a carcinogenic group (n = 30), a NIM group (n = 30), a diet control group (n = 8) and a NIM control group (n = 8). The levels of COX-2 mRNA and protein in each group were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The contents of prostaglandin E2 (PGE2) in plasma and tumor tissues were determined by radioimmunoassay. TUNEL Act, proliferating cell nuclear antigen were detected apoptosis and proliferation index. Results The incidence of breast cancer in NIM group (40.3%) was significantly lower than that in carcinogenic group (69.2%). COX-2 mRNA and protein levels in NIM group were significantly lower than those in carcinomatous group [A value: 0.21 ± 0.05 vs. 0.46 ± (P <0.05); (30.26 ± 8.75) vs. (58.13 ± 10.02), P <0.05]. The levels of PGE2 in plasma and tumor tissues were significantly lower than those in control group [(233 ± 59) pg / ml vs pg / ml, P <0.01; (167 ± 42) pg / mg protein vs. (250 ± 67) pg / mg protein, P <0.05]. The proliferation index of tumor cells in NIM group decreased (P <0.01). There was a significant difference between the two groups (P <0.01). The difference was statistically significant (P <0.01). Conclusion NIM inhibits the synthesis of prostaglandins, inhibits the proliferation of tumor cells, induces apoptosis and reduces the incidence of DMBA-induced breast cancer in rats by down-regulating the expression of COX-2.