As <sub> 2 </ Sub> O <sub> 3 </ Sub> The Study Of Human Breast Cancer Xenografts In Nude Mice

Objective To investigate the antitumor activity of arenic trioxide on a heterologous graft model for human breast infiltrating duct carcinoma in nude mice.Methods Completely random design, mice bearing tumor were divided into four groups, control normal saline, group 1 (As2O31.5mg?kg-1?d-1), group 2 (As2O33.0mg?kg-1?d-1), group DDP, which were injected by a tail vein for 7 days. Then, the inhibitory effect of medicines on the growth of tumor was observed by blood cell count , bone marrow smear , TEM and FCM. Their expression of Ki67 and bcl-2 were detected by immunohitochemistry. Cell apoptosis in situ was examined by a TUNEL assay in the samples of carcinoma.Result ①After the administration of As2O3 1.5mg?kg-1?d-1 and 3.0mg?kg-1?d-1, the growth of solid tumor were obviously inhibited. Theinhibitory rate were 79.69% and 78.18% respectively, but there was no significant difference (P>0.05). After the administration of DDP, the growth of solid tumor were also obviously inhibited. The inhibitory rate were 54.55%, there was significant difference between group DDP and groups As2O3 (P<0.05). ②Under the inspection of transmission electron microscope, the cells of the solid tumor showed the typically morphological characteristics of apoptosis. ③The sub-G1 peaks of group 1 and group 2 were observed by flow cytometry on solid tumor speciman and the apoptotic rate were 12.6% and 40.6% respectively. The number of DNA in bone marrow of group 1 and group 2 were more than that of the others. ④The Ki67-LI of group 1, group 2 and group DDP was lower than that of group normal saline (P<0.05). But it hadn't significant difference between group 1, group 2 and group DDP (P>0.05). These indicated that As2O3 could inhibit the proliferation of graft tumor cell.⑤Immunohistochemical staining of bcl-2 showed significant difference between four groups (P<0.05), which indicated that As2O3 could inhibit the expression of bcl-2 in graft tumor cells. ⑥Detection of cell apoptosis in situ by a TUNEL assay showed that AI has significant difference between four groups (P<0.05). The AI of group 1 and group 2 was more much than that of group DDP and group normal saline(P<0.05). The AI of group 2 was more much than that of group 1 (P<0.05). ⑦Treatment with As2O3 was no side effect. The function of hematopoietic system wasn't inhibited. But the weight of nude mice in group DDP decreased obviously than that of the others. The leukocytopenia was also significant in group DDP. Conclusion Arenic trioxide has obvious antitumor activity on a heterologous graft model for human breast infiltrating duct carcinoma in nude mice. The side effects weren't obviously.