丛生蛋白反义核苷酸对裸鼠人膀胱癌模型的肿瘤抑制作用

Targeted therapy of human bladder cancer in a nude mice model by clusterin antisense oligodeoxynucleotide

目的观察单独使用丛生蛋白反义寡聚脱氧核苷酸(clusterin ASO)以及联合应用化疗药物吉西他滨对裸鼠人膀胱癌T24细胞生长的影响。方法将32只裸鼠随机分为空白对照组,clusterin ASO组,吉西他滨组和clusterin ASO+吉西他滨组(每组8只)。每只裸鼠右侧肩部皮下接种T24细胞,各组相应瘤体内注射clusterin ASO,尾静脉注射吉西他滨,连续观察6周肿瘤细胞的生长变化。结果Clusterin ASO组和吉西他滨组裸鼠生存期延长,肿瘤体积得到抑制。Clusterin ASO+吉西他滨组肿瘤抑制明显,抑瘤率达94.68%。结论膀胱癌T24细胞在裸鼠体内的生长能被clusterin ASO所抑制。联合应用clusterin ASO和吉西他滨不仅对T24细胞在裸鼠皮下肿瘤的生长具有抑制作用,同时还可使肿瘤体积缩小,并可能增加T24细胞对吉西他滨的化疗敏感性。

Objective To observe the effects of clusterin antisense oligodeoxynucleotide （ASO） only or combined with gemcitabine on human bladder carcinoma line T24 in a nude mice model, and to explore the mechanism and significance of anti clusterin gene therapy for bladder carcinoma. Methods Thirty-two nude mice were divided into 4 groups randomly as control group, clusterin ASO group, gemcitabine group, and clusterin ASO combined with gemcitabine group （n = 8 for each group）. The animal model was established by injecting human bladder carcinoma cell line T24 into the right shoulder of nude mice subcutaneously. The clusterin ASO was injected into the tumor of nude mice, and the gemcitabine was injected into the caudal vein of nude mice. Then the growth of T24 cell was observed continuously for six weeks. Results The life span of nude mice in clusterin ASO group and gemcitabine group were extended and the growth of T24 cell were slightly inhibited. The inhibition of clusterin ASO combined with gemcitabine group was significant with a inhibition rate of 94.68%. Conclusions The elusterin ASO is effective in the therapy of human bladder carcinoma cell line T24, and this effect could be enhanced when combined with gemcitabine. Knockdown of the expression of elusterin by elusterin ASO might increase the sensitivity of bladder cancer cells to gemeitabine.