紫花牡荆素对人宫颈癌裸鼠移植瘤生长的影响及其机制

摘要

Objective To investigate the effects of Casticin (CAS) on the growth of human cervical carcinoma HeLa cells xenografts in nude mice and its possible molecular mechanism. Methods Models of human cervical cancer HeLa cells xenografts transplanted subcuta-neously in nude mice were established and randomly divided into five groups(each group including five nude mice):saline group, Cispla-tin group, low dose CAS group, middle dose CAS group and high dose CAS group. Tumor volume and tumor weight were observed and compared. The alteration of the weight of nude mice, and the change of serum levels of LDH, ALT, Cr and WBC counts were examined and compared. The rate of apoptotic cells of human cervical carcinoma HeLa cells xenografts was analyzed by PI stained FCM. The ex-pressions of cyclin B1 protein and p21 protein of HeLa cells xenografts were determined by western blot. Results CAS could significantly suppress the increasing volume and weight of human cervical carcinoma HeLa cells xenografts in nude mice models in time and dose de-pendent manner, yet had no significant effect on the weight of nude mice, the serum levels of LDH, ALT, Cr and WBC counts. When the xenografts cells treated with CAS for 16 days, the apoptotic rate of xenografts cells increased in a dose-dependent manner, and the expression of p21 protein was up-regulated and protein level of cyclin B1 was decreased. Conclusions CAS could suppress the growth of human cervical carcinoma HeLa cells xenografts in nude mice, which may be related to its promotion on xenografts cell apoptosis through down-regulation of cyclin B1 expression and activation of p21 expression.%目的：研究紫花牡荆素（CAS）对人宫颈癌HeLa细胞裸鼠移植瘤生长的影响及其机制。方法建立人宫颈癌HeLa细胞裸鼠皮下移植瘤模型，并随机分成5组，每组5只：生理盐水组、顺铂组、低剂量CAS组、中剂量CAS组和高剂量CAS组。观察和比较各组裸鼠移植瘤的体积和重量，裸鼠体重的变化，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分析瘤组织细胞内p21和cyclin B1的蛋白表达。结果 CAS可显著抑制人宫颈癌HeLa细胞裸鼠移植瘤的体积和重量的增加，呈作用剂量和时间依赖性；而对裸鼠的体重、谷丙转氨酶、乳酸脱氢酶、肌酐值和外周血白细胞计数均无明显的影响。CAS作用16天后，裸鼠移植瘤细胞的凋亡率呈剂量依赖性增加，cyclin B1的蛋白表达降低，p21的蛋白表达增高。结论 CAS具有抑制人宫颈癌裸鼠移植瘤生长的作用，可能与其降低cyclin B1的蛋白表达，增加p21的蛋白表达，促进细胞凋亡有关。