丙泊酚对人胃癌裸鼠移植瘤生长的影响

Effect of Propofol on growth of human gastric cancer xenografts in nude mice

摘要:

目的 探讨丙泊酚对人胃癌裸鼠移植瘤生长的影响，及其可能的作用机制。方法 培养人胃癌 细胞株SGC7901，复制裸鼠移植瘤模型30 只，随机分为对照组、生理盐水组和丙泊酚组，每组10 只。对照 组未做任何处理；生理盐水组腹腔注射生理盐水1.5 ml/kg ；丙泊酚组腹腔注射丙泊酚20 mg/kg，1 次/d，连 续2 周。观察各组裸鼠给药前后一般情况的变化，给药后每3 d 用游标卡尺测量移植瘤的长径和短径，计算移 植瘤体积。第15 天时将裸鼠脱臼处死，剥离瘤体。采用实时荧光定量聚合酶链反应和Western blot 检测各组 裸鼠移植瘤组织中核因子E2 相关因子2（Nrf2）、NAD（P）H 醌氧化还原酶1（NQO1）、血红素加氧酶-1 （HO-1）、B 淋巴细胞瘤（Bcl-2）、Bcl-2 相关X 蛋白（Bax）基因和蛋白的表达。结果 丙泊酚组裸鼠给药 后3、6、9、12 和15 d 的移植瘤体积小于对照组和生理盐水组（P <0.05）。与对照组和生理盐水组相比，丙 泊酚组裸鼠移植瘤体质量降低，而抑瘤率升高（P <0.05）。与对照组和生理盐水组相比，丙泊酚组裸鼠移植瘤 组织中Nrf2、NQO1、HO-1、Bcl-2 mRNA 和蛋白相对表达量降低，而Bax mRNA 和蛋白相对表达量升高 （P <0.05）。结论 丙泊酚可抑制人胃癌裸鼠移植瘤的生长，其机制可能与抑制Nrf2/ARE 信号通路，从而促 进细胞凋亡有关。

Abstract:

Objective To investigate the effect of Propofol on growth of human gastric cancer xenografts in nude mice and the possible mechanisms. Methods Human gastric cancer cell line SGC7901 was cultured. The models of subcutaneous tumor were established in thirty BALB/c nude mice, and randomly divided into a control group, a saline group and a Propofol group. The mice in the control group did not receive any treatment, those in the saline group were given intraperitoneal injection of saline 1.5 ml/kg once a day for 2 consecutive weeks, while the mice in the Propofol group received Propofol 20 mg/kg once a day for 2 consecutive weeks. The changes of the general condition of the nude mice before and after administration were observed. The caliper was used to measure the tumor size every 3 days after administration, and the tumor volume was calculated. The nude mice were sacrificed on the 15th d, and the tumors were isolated. The expressions of nuclear factor E2-related factor 2 (Nrf2 ), NAD(P)Hquinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1 ), B-cell lymphoma-2 (Bcl-2 ), Bcl-2 associated X protein (Bax ) genes and proteins in the tumor tissues of different groups were detected using qRT-PCR and Western blot, respectively. Results The tumor volume in the Propofol group was smaller than that in the control group and the saline group 3, 6, 9, 12 and 15 d after administration, the differences were statistically significant (P < 0.05). Compared with the control group and the saline group, the tumor weight was decreased, while the tumor inhibition rate was increased in the Propofol group, the differences were statistically significant (P < 0.05). Compared with the control group and the saline group, the relative expression levels of Nrf2 , NQO1, HO-1 and Bcl-2 mRNAs and proteins in the tumor tissues were decreased, while the relative expression levels of Bax mRNA and protein were increased in the Propofol group, the differences were statistically significant (P < 0.05). Conclusions Propofol could inhibit the growth of human gastric cancer xenografts in nude mice. The mechanism may be related to inhibition of Nrf2/ARE signaling pathway to promote apoptosis.