As_2O_3对人乳腺癌移植瘤增殖凋亡的影响

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

目的 :观察As2 O3 对人乳腺癌裸鼠移植瘤的增殖和凋亡作用 .方法 :建立人乳腺癌裸鼠移植瘤的模型 ,随机分为4组 ,经尾静脉iv用药 7d ,观察各组动物及肿瘤的情况 .结果 :①实验组 1、2和顺铂组的肿瘤标本中均可见有明显的凋亡峰 ,凋亡率分别是 1 2 .6 %、4 0 .0 %和 1 1 .3% .实验组 1、2的异倍体峰明显低于阴性对照组和顺铂组 .②实验组 1、2和顺铂组的Ki 6 7 LI比阴性对照组低 ,有显著性差异 (P <0 .0 5 ) .但实验组 1、2和顺铂组之间差异无显著性 (P >0 .0 5 ) .实验组 1、2的bcl 2表达低于阴性对照组、顺铂组 (P <0 .0 5 ) .③实验组 1、2比阴性对照组、顺铂组的凋亡指数高 (P <0 .0 5 ) .实验组 2比实验组 1的凋亡指数高 (P <0 .0 5 ) .④在用药期间As2 O3 对鼠造血系统功能影响不大 .As2 O3 亦不影响裸鼠体质量的增加 .结论 :As2 O3 对人乳腺癌裸鼠移植瘤有明显抑制肿瘤细胞增殖生长、下调肿瘤细胞bcl 2的表达、诱导肿瘤细胞凋亡的作用 。

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), As 2O 3 group 1 (1.5 mg/kg per day) ( n =6), As 2O 3 group 2 (3.0 mg/kg per day) ( n =6) and DDP group (cis Diaminedichloroplatinum) ( 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 Ki 67 and bcl 2 was detected by immunohitochemistry and cell apoptosis in situ was examined by a TUNEL assay in the samples of carcinoma. RESULTS: ① After the administration of As 2O 3 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 As 2O 3 groups ( P <0.05). The sub G1 peaks of As 2O 3 group 1 and As 2O 3 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 As 2O 3 groups decreased more than those of other groups. ② The Ki 67 LI of As 2O 3 groups and DDP group was lower than that of the normal saline group ( P <0.05). But no difference was found between As 2O 3 groups and DDP group ( P >0.05). These indicated that As 2O 3 could inhibit the proliferation of graft tumor cells. ③ Immunohistochemical staining of bcl 2 showed significant difference between the four groups ( P <0.05), which indicated that As 2O 3 could inhibit the expression of bcl 2 in graft tumor cells. ④ 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 As 2O 3 groups was much higher than that of DDP group and normal saline group ( P <0.05). The AI of As 2O 3 group 2 was much higher than that of As 2O 3 group 1 ( P <0.05). ⑤ The function of hematopoietic system was not inhibited during treatment with As 2O 3. As 2O 3 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 bcl 2 and induce tumor cell apoptosis, with little obvious side effects.