顺铂联合8-硝基白杨素对人卵巢癌细胞裸鼠移植瘤生长的影响

Effect of 5,7-Dihydroxyl-8-nitrio Chrysin Combination with Cisplatin on the Growth of Human Ovarian Carcinoma COC1 Cells Xenografts in Nude Mice

关键词:  卵巢癌  8-硝基白杨素  顺铂  移植瘤  凋亡

Key words:  ovarian cancer  8-NOChR  cisplatin  xenografts  apoptosis

摘要:

目的 研究顺铂联合8-硝基白杨素对人卵巢癌COC1细胞裸鼠移植瘤生长的影响。方法 建立人卵巢癌COC1细胞裸鼠皮下移植瘤模型，随机分成4组，每组5只：生理盐水组、8-硝基白杨素组、顺铂组、8-硝基白杨素+顺铂组。观察各组裸鼠移植瘤体积、重量及裸鼠体质量的变化；裸鼠血清乳酸脱氢酶、谷丙转氨酶、肌酐值和外周血白细胞计数的变化；FCM测定瘤组织细胞凋亡率；Western blot分析瘤组织细胞凋亡的可能分子生物学机制。结果 与顺铂组和8-硝基白杨素组相比，顺铂联合8-硝基白杨素联合作用COC1细胞裸鼠移植瘤后，移植瘤的体积、移植瘤的重量均明显降低(P<0.05)；与顺铂组相比，顺铂联合8-硝基白杨素联合组裸鼠体质量无明显差异(P>0.05)，裸鼠血清乳酸脱氢酶、谷丙转氨酶、肌酐值和外周血白细胞计数无明显差异(P>0.05)；顺铂和8-硝基白杨素联合作用COC1细胞16 d后，COC1细胞发生凋亡，同时bcl-2蛋白表达降低，caspase-3蛋白表达增高。结论 顺铂联合8-硝基白杨素通过降低bcl-2蛋白表达，活化caspase-3蛋白表达来抑制人卵巢癌COC1细胞裸鼠移植瘤生长。

Abstract:

OBJECTIVE To investigate the effect of 5,7-dihydroxyl-8-nitrio chrysin(8-NOChR) combination with cisplatin(DDP) on the growth of human ovarian carcinoma COC1 cells xenografts in nude mice. METHODS Models of human ovarian cancer COC1 cells xenografts transplanted subcutaneously in nude mice were established, and randomly divided into four groups: saline group, 8-NOChR group, DDP group, 8-NOChR combination with DDP group. Tumor volume, tumor weight and the weight of nude mice were measured. The serum levels of LDH, ALT, Cr and WBC counts were determined. The rate of apoptotic cells of human ovarian carcinoma COC1 cells xenografts was analyzed by PI stained FCM. The expressions of bcl-2 protein and caspase-3 protein of COC1 cells xenografts were determined by Western blot. RESULTS There were significant difference in tumor volume and tumor weight between the nude mice treated with 8-NOChR combined with DDP and those treated with 8-NOChR or DDP(P<0.05). There were no difference in the weight of nude mice and in the serum levels of LDH, ALT, Cr and WBC number in the nude mice treated 8-NOChR combined with DDP comparing with those treated with DDP(P>0.05). The xenografts cells treated with 8-NOChR combined with DDP showed apoptosis. Western blot showed that expression of caspase-3 protein was upregulated and protein level of bcl-2 was depressed after treatment with 8-NOChR combined with DDP. CONCLUSION 8-NOChR and DDP have synergistic effects on the growth inhibition of human ovarian carcinoma COC1 cells xenografts in nude mice. Mechanism may be downregulation of bcl-2 expression and activation of caspase-3 expression