Abraxne 对Lewis 肺癌小鼠Per 2 基因 及SIRT1 因子表达的影响

Influence of Abraxne on Per2 and SIRT1 gene expressions in mice with Lewis lung cancer

摘要:

目的 探讨白蛋白结合型紫杉醇（Abraxne）对Lewis 肺癌模型小鼠生物钟基因Per 2、沉默信息 调节因子1（SIRT1）表达的影响。方法 将60 只SPF 级C57BL/6 雌性小鼠随机分为正常对照组、模型组、 紫素组[ 紫素30 mg/（kg·d）]、Abraxne 组[Abraxne 30 mg/（kg·d）]，每组15 只。除正常对照组外，其他 各组小鼠于右腋部背侧皮下接种Lewis 肺癌细胞（LLC）复制Lewis 肺癌小鼠模型。于接种后第5 天开始尾 静脉注射给药，连续用药10 d，观察各组小鼠体重、肿瘤体积及生物学行为变化。采用实时荧光定量聚合酶 链反应和Western blot 检测肿瘤组织中Per2、SIRT1 mRNA 和蛋白的表达。结果 4 组小鼠接种LLC 细胞 前、接种后第5 天、给药后第5 和10 天的体重变化比较，结果显示：①不同时间点的体重有差别（F =17.703， P =0.000）；② 4 组小鼠体重有差别（F =7.976，P =0.000）；③ 4 组小鼠体重变化趋势有差别（F =21.641， P =0.000）。模型组、紫素组、Abraxne 组小鼠给予Abraxne 治疗后第0、2、4、6、8 和10 天的肿瘤体积比较， 结果显示：①不同时间点的肿瘤体积有差别（F =35.128，P =0.000）；② 3 组小鼠肿瘤体积有差别（F =8.376， P =0.000）；③ 3 组小鼠肿瘤体积变化趋势有差别（F =43.624，P =0.000）。与模型组比较，紫素组和Abraxne 组小鼠肿瘤组织中Per2、SIRT1 mRNA 和蛋白表达水平升高（P <0.05），且Abraxne 组小鼠肿瘤组织中Per2、 SIRT1 mRNA 和蛋白表达水平高于紫素组（P <0.05）。结论 Abraxne 较紫素更能抑制Lewis 肺癌小鼠肿瘤 生长，其机制可能与生物钟基因Per 2、SIRT 1 的表达被强化有关。

Abstract:

Objective To explore the influence of albumin-bound paclitaxel (Abraxne) on the expressions of circadian clock genes Per2 and SIRT1 in Lewis lung cancer model mice. Methods Sixty C57BL/6 female mice of SPF grade were randomly divided into a normal control group, a model group, a paclitaxel group [30 mg/(kg·d)] and an Abraxne group [30 mg/(kg·d)], with 15 rats in each group. Lewis lung cancer mouse model was established by subcutaneous injection of Lewis lung cancer cells (LLC) into the right axillary dorsal skin of all mice except the normal control group. From the 5th d after inoculation, intravenous drug injection was started through the tail vein for 10 days continuously. The changes of body weight, tumor volume and biological behavior of the mice in each group were observed. The expressions of Per2 and SIRT1 mRNAs and proteins in the tumor tissues were detected by qRT-PCR and Western blot. Results The changes of body weight were compared among the 4 groups before LLC inoculation, on the 5th d after inoculation, and 5 and 10 d after drug administration, the results showed that the body weight was different at different time points (F = 17.703, P = 0.000), the body weight was different among the 4 groups (F = 7.976, P = 0.000), the change trends of body weight were different among the 4 groups (F = 21.641, P = 0.000). The tumor volume was compared among the model group, the paclitaxel group and the Abraxne group on the 0, 2nd, 4th, 6th, 8th and 10th d after Abraxne administration, the results showed that the tumor volume was different at different time points (F = 35.128, P = 0.000), the tumor volume of the 3 groups was different (F = 8.376, P = 0.000), the change trends of the tumor size were different among the 3 groups (F = 43.624, P = 0.000). Compared with the model group, Per2 and SIRT1 mRNA and protein expressions in the paclitaxel group and the Abraxne group were significantly increased (P < 0.05), in which the Per2 and SIRT1 mRNA and protein expressions in the Abraxne group were significantly higher than those of the paclitaxel group (P < 0.05). Conclusions Abraxne can inhibit the growth of Lewis lung cancer in mice more significantly than paclitaxel. Its mechanism may be related to the enhanced expressions of circadian clock genes Per2 and SIRT1 .