奥曲肽和三苯氧胺治疗二甲基苯蒽诱发大鼠乳腺癌的实验研究

Effect of tamoxifen plus octreotide on DMBA-induced mammary tumors in rats

目的 探讨生长抑素类似物奥曲肽(OCT)和三苯氧胺(TAM)的体内抗乳腺癌作用。方法 将接受致癌剂二甲基苯蒽(DMBA, 100mg/kg,一次性皮下注射)后8周的96只Wistar雌鼠,随机分为对照组(单纯诱发组),OCT组( 100μg/kg, 2次/日皮下注射,共14周),TAM组( 1mg/kg,5次/周皮下注射,共14周)和OCT加TAM组,每组24只。观察乳腺肿瘤发生的潜伏期、诱发率,每只大鼠乳腺肿瘤的个数和体积,并利用光镜、电镜进行肿瘤细胞形态学和超微结构研究。结果 (1)乳腺肿瘤平均潜伏期:TAM组(119d±19d)和OCT加TAM组(120d±16d)明显长于对照组(90d±17d)和OCT组(102d±15d) (均P<0 .05); (2)乳腺肿瘤诱发率:OCT加TAM组(23 .8% )、TAM组(45 .5% )、OCT组(52. 4% )均明显低于对照组(70% ) (均P<0 .05 ),而OCT加TAM组明显低于OCT组和TAM组(均P<0 .05); (3)乳腺肿瘤个数:对照组明显高于其余3组(均P<0 .05),OCT加TAM组明显低于OCT组和TAM组(均P<0 .05); (4)注射致癌剂后22周乳腺肿瘤平均体积:对照组(6434mm3 ±1536mm3 )明显高于OCT组(4366mm3 ±1213mm3 )、TAM组(41.38mm3 ±10.91mm3 )和OCT加TAM组(12.85mm3 ±3.29mm3 ) (均P<0 .05),OCT加TAM组明显低于TAM组和OCT组(均P<0 .01);实验18周时TAM组乳腺肿瘤体积(1126mm3 )

Objective To further study the antitumor effects of TAM and somatostatin (SST) analog octreotide (OCT) in vivo.Methods Eight weeks following dimethylbenzanthracene (DMBA,a single dose 100 mg/kg by subcutaneous injection) adiministration, 96 Wistar rats were randomly divided into four groups: control group, OCT(100 μg/kg bid for 14 weeks by subc utaneous injection) group, TAM(1 mg/kg 5 times weekly for 14 weeks by subcutaneo us injection) group and OCT+TAM group. The mean latent phases of mammary tumori genesis and incidence of mammary tumor-positive rats were observed. The number and volumes of tumors per animal were measured. The histological structures and ultrastructures of mammary samples were observed by using a light microscopy and a transmission electron microscopy.Results (1) The latent phases of mamary tumorigenesis in the TAM group and th e OCT +TAM group were significantly longer than those in the control or OCT grou p (all P<0.05). (2) The incidence of mammary tumor-positive rats were 70% in the control group, 52.4% in the OCT group, 45.5% in TAM group and 23.8% i n the OCT+TAM group respectively, significantly longer in the three treated grou ps(P<0.05 or P<0.01), and the differences between the OCT+TAM group and the OCT group or TAM group were significant(both P<0.05). (3) The nu mbers of mammary tumors per rat were markedly less in the three treated groups t han in the control group(P<0.05 or P<0.01), and there were significan tly differences between the OCT+TAM group and the OCT group or TAM group(all P<0.05). (4) The mean volumes of mammary tumors per rat were significantly greater in the control group (6434mm3) than in the three treated groups group (P<0.05 or P<0.01), but the tumor volume in the OCT+TAM group (1285 mm3) was less than those in the OCT group (4366 mm3) or TAM group(4138 mm 3) (P<0.01). At 10th week of treatment the mean volume was obviously sma ller in TAM group than in OCT group(P<0.05), but at 14th week of treatmen t the difference was not significant (P>0.05). (5) Histopathological examin ation revealed that the mammary tumors in the OCT+TAM group were more differenti ated and exhibited a less aggressive phenotype, compared with the tumors growing in the control group. Conclusion Both OCT and TAM inhibit the tumorigenesis and development of DMBA-i nduced mammary tumors, however, resistance to TAM may appear during TAM treatmen t. Combination of OCT and TAM has significant synergetic antitumor effect. TAM in combination with OCT may bacome be an efficient hormone therapy means for br east cancer patients.