Effect of arsenic trioxide on proliferation and apoptosis of a heterologous graft in nude mice bearing human breast infiltrating duct carcinoma

    CHEN Xin, WU Chengª²Yi

    First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400016, China

    ¡¾Abstract¡¿ AIM: To investigate the effects of arsenic trioxide on the proliferation and apoptosis of a heterologous graft in nude bearing mice human breast infiltrating duct carcinoma. METHODS: Mice bearing tumor were randomly divided into four groups: Control group (normal saline) (n = 5), As2O3 group 1 (1.5 mg/kg per day) (n=6), As2O3 group 2 (3.0 mg/kg per day) (n=6) and DDP group (cisª²Diaminedichloroplatinum) (n=5), and all groups received injection by a tail vein for 7 days. The inhibitory effects of medicines on the growth of tumor were observed by FCM, the expression of Kiª²67 and bclª²2 was detected by immunohitochemistry and cell apoptosis in situ was examined by a TUNEL assay in the samples of carcinoma. RESULTS: ¢Ù After the administration of As2O3 1.5 mg/kg and 3.0 mg/kg per day, the growth of solid tumor was obviously inhibited. The inhibitory rate was 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 was also obviously inhibited. The inhibitory rate was 54.55% and there was significant difference between DDP group and As2O3 groups (P<0.05). The subª²G1 peaks of As2O3 group 1 and As2O3 group 2 and DDP group were observed by flow cytometry on solid tumor specimen and the apoptotic rate was 12.6%, 40.0% and 11.3% respectively. DNA aneuploid peaks of As2O3 groups decreased more than those of other groups. ¢Ú The Kiª²67ª²LI of As2O3 groups and DDP group was lower than that of the normal saline group (P<0.05). But no difference was found between As2O3 groups and DDP group (P>0.05). These indicated that As2O3 could inhibit the proliferation of graft tumor cells. ¢Û Immunohistochemical staining of bclª²2 showed significant difference between the four groups (P<0.05), which indicated that As2O3 could inhibit the expression of bclª²2 in graft tumor cells. ¢Ü Detection of cell apoptosis in situ by a TUNEL assay showed that the apoptosis index(AI) had significant difference between the four groups (P<0.05). The AI of As2O3 groups was much higher than that of DDP group and normal saline group (P<0.05). The AI of As2O3 group 2 was much higher than that of As2O3 group 1 (P<0.05). ¢Ý The function of hematopoietic system was not inhibited during treatment with As2O3. As2O3 had no effect on the weight of nude mice. CONCLUSION: Arenic trioxide has obvious antitumor effects on a heterologous graft in nude mice bearing human breast infiltrating duct carcinoma and it can adjust the expression of bclª²2 and induce tumor cell apoptosis, with little obvious side effects. ......