三苯氧胺联合塞来昔布预防大鼠乳腺癌发生的实验研究

背景与目的:三苯氧胺能有效预防乳腺癌的发生,但并非全部有效。多种肿瘤细胞表达环氧化酶-2(cyclooxygenase-2,COX-2),其表达与肿瘤的发生发展有关。本研究观察三苯氧胺联合COX-2选择性抑制剂塞来昔布对化学致癌剂7,12-二甲基苯蒽(7,12-dimethybenzanthracene,DMBA)诱发的大鼠乳腺癌形成的影响。方法:DMBA油剂灌胃制备大鼠乳腺癌模型,每组30只大鼠,分为单纯诱癌组、三苯氧胺组、塞来昔布组和联合药物组4组,观察各组肿瘤发生率、潜伏期、肿瘤数目及体积的差异。结果:(1)乳腺肿瘤发生率三苯氧胺组(48.15%,13/27)、塞来昔布组(50.00%,14/28)低于单纯诱癌组(85.71%,24/28),高于联合药物组(21.43%,6/28);(2)乳腺肿瘤发生时间三苯氧胺组[(97.54±1.85)天]、塞来昔布组[(96.79±2.89)天]晚于单纯诱癌组[(89.50±5.99)天],早于联合药物组[(103.67±3.39)天];(3)乳腺肿瘤数目三苯氧胺组[(1.77±0.73)个]、塞来昔布组[(1.71±0.61)个]小于单纯诱癌组[(3.50±1.62)个],大于联合药物组[(1.17±0.42)个];(4)乳腺肿瘤体积三苯氧胺组[(1.78±0.71)cm3]、塞来昔布组[(2.05±1.04)cm3]小于单纯诱癌组[(6.42±3.96)cm3],大于联合药物组[(0.71±0.96)cm3],且均有统计学意义(均为P<0.05)。结论:塞来昔布和三苯氧胺能抑制DMBA诱发的大鼠乳腺癌的发生、发展,两者联合使用效果更好。

Chemopreventive effect of tamoxifen combined with celecoxib on DMBA-induced breast cancer in rats

BACKGROUND & OBJECTIVE: Breast cancer can be prevented partly by tamoxifen. Cyclooxygenase-2 (COX-2) is expressed in many kinds of tumors, and correlated to the occurrence and progress of tumors. This study was to evaluate the chemopreventive effect of tamoxifen combined with celecoxib, a COX-2 selective inhibitor, on 7,12-dimethylbenz anthracene (DMBA)-induced breast cancer in rats. METHODS: DMBA was irrigated into the stomach of SD female rats to build breast cancer model. The rats were divided into 4 groups: control group, tamoxifen group, celecoxib group, and combination group; each group contained 30 rats. Tumor occurrence, latency period, number and volume of breast cancer were observed. RESULTS: The tumor occurrence rates in tamoxifen group (48.15%, 13/27) and celecoxib group (50.00%, 14/28) were lower than that in control group (85.71%, 24/28), and higher than that in combination group (21.43%, 6/28). The latency periods of tamoxifen group [(97.54+/-1.85) days] and celecoxib group [(96.79+/-2.89) days] were longer than that of control group [(89.50+/-5.99) days], and shorter than that of combination group [(103.67+/-3.39) days]. The tumor numbers of tamoxifen group (1.77+/-0.73) and celecoxib group (1.71+/-0.61) were less than that of control group (3.50+/-1.62), and more than that of combination group (1.17+/-0.42). The tumor volumes of tamoxifen group [(1.78+/-0.71) cm(3)] and celecoxib group [(2.05+/-1.04) cm(3)] were smaller than that of control group [(6.42+/-3.96) cm(3)], and larger than that of combination group [(0.71+/-0.96) cm(3)]. All differences were significant (P<0.05, respectively). CONCLUSION: Celecoxib and tamoxifen could effectively prevent the occurrence of DMBA-induced breast cancer in rats; the combination of them has better chemopreventive effect.