二氧化硒联合顺铂对裸鼠皮下耐药细胞株SKOV3/CDDP移植瘤的影响及其作用机制

Effect of selenium dioxide united DDP on the human ovarian cancer cells xenografts in nude mice and its mechanism

目的探讨二氧化硒(SeO2)联合顺铂(DDP)对裸鼠皮下耐药细胞株SKOV3/CDDP移植瘤的影响及其可能的作用机制。方法将人卵巢癌SKOV3/CDDP细胞接种于SPF级雌性BALB/C裸鼠皮下,随机分成治疗组和对照组。治疗组分为DDP组、SeO2组、DDP联合SeO2组,分别给予DDP、SeO2、DDP+SeO2腹腔注射,对照组给予生理盐水,观察各组成瘤率、生长率、平均抑瘤率,绘制肿瘤生长曲线。用流式细胞术检测肿瘤细胞的凋亡程度、HE染色和免疫组化染色法检测肿瘤细胞P糖蛋白(P-gp)的表达。结果 DDP组、SeO2组、DDP联合SeO2组的平均抑瘤率分别为48.29%、41.69%、72.28%,肿瘤平均细胞凋亡率分别为25.92%、24.14%、45.43%,DDP联合SeO2组与其他治疗组的抑瘤率、细胞凋亡率比较差异有统计学意义(P均<0.05),且其S期细胞明显减少。SeO2组、DDP联合SeO2组P-gp的阳性表达水平明显低于DDP组及对照组(P均<0.05)。结论 SeO2和DDP对诱导耐药卵巢癌细胞凋亡有协同作用,SeO2可能通过降低P-gp的阳性表达来增加耐药卵巢癌对DDP的敏感性。

Objective To investigate the effect of the combination of selenium dioxide and cisplatin on the human o- varian cancer cells xenografts in nude mice and its mechanism. Methods Human ovarian cancer models were established by subcutaneously transplanting SKOV3/CDDP cells into nude mice, then dividing them into control group and treatment group. The treatment group were divided into DDP group, SeO2 group, DDP ＋ SeO2 group. Sodium chloride was given in control group. Then the transplantation rate, growth rate, mean tumor inhibition rate and weight, appetite and mental state of the nude mice in different groups were observed. Flow cytometry was used to assess the degree of apoptosis in the tissues of the tumor. The level of P-gp in tumor cells was detected by HE staining and immunohistochemical method. Results Mean tumor inhibition rate in DDP group, SeO2 group,DDP ＋ SeO2 group was separately 48.29% , 41.69% , 72.28%, mean apoptosis rate separately 25.92% , 24.14% , 45.43%. The mean tumor inhibition rate and mean apoptosis rate in the DDP ＋ SeO2 group were higher than those in DDP group or SeO2 group （ P 〈 O. 05 ）. The cancer cells in the S phase were decreased in DDP ＋ SeO2 group. The P-gp levels in SeO2 group and DDP ＋ SeO2 group were lower than those in DDP group （ P 〈 0.05 ）. Conclusions SeO2 and DDP have united effect on apoptosis of drug-fast ovarian, and SeO2 can inhibit the expression of P-g＇p, which may be one of the important mechanism of adding the sensitivity of drug-fast oophoroma to DDP.