[Effect of tamoxifen plus octreotide on DMBA-induced mammary tumors in rats].
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) administration, 96 Wistar rats were randomly divided into four groups: control group, OCT (100 microg/kg bid for 14 weeks by subcutaneous injection) group, TAM (1 mg/kg 5 times weekly for 14 weeks by subcutaneous injection) group and OCT + TAM group. The mean latent phases of mammary tumorigenesis 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 mammary tumorigenesis in the TAM group and the OCT + TAM group were significantly longer than those in the control or OCT group (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% in the OCT + TAM group respectively, significantly longer in the three treated groups (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 numbers of mammary tumors per rat were markedly less in the three treated groups than in the control group (P < 0.05 or P < 0.01), and there were significantly 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 (6434 mm(3)) than in the three treated groups group (P < 0.05 or P < 0.01), but the tumor volume in the OCT + TAM group (1285 mm(3)) was less than those in the OCT group (4366 mm(3)) or TAM group (4138 mm(3)) (P < 0.01). At 10th week of treatment the mean volume was obviously smaller in TAM group than in OCT group (P < 0.05), but at 14th week of treatment the difference was not significant (P > 0.05). (5) Histopathological examination revealed that the mammary tumors in the OCT + TAM group were more differentiated and exhibited a less aggressive phenotype, compared with the tumors growing in the control group.


CONCLUSIONS
Both OCT and TAM inhibit the tumorigenesis and development of DMBA-induced mammary tumors, however, resistance to TAM may appear during TAM treatment. Combination of OCT and TAM has significant synergetic antitumor effect. TAM in combination with OCT may become be an efficient hormone therapy means for breast cancer patients.
Zeng
Xi-Zhi
XZ
Department of General Surgery, First Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing 400016, China.
Yao
Zhen-Xiang
ZX
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D015282:Octreotide / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; D015282:Octreotide