摘要
目的:探讨益气除痰方对BALB/c裸小鼠肺癌A549移植瘤的抑制作用及其机制。方法:人肺腺癌细胞A549接种BALB/c裸鼠40只,随机分为模型组(生理盐水)、顺铂注射液(0.002 g/kg)组、益气除痰方低剂量(3.0g/kg)组、益气除痰方高剂量(6.0 g/kg)组、联合用药(益气除痰方6.0 g/kg+顺铂注射液组0.002 g/kg)组。造模第8天,中药灌胃,1次/d,每次0.2 m L,连续14 d。第17天,顺铂注射液腹腔注射,1次/d,每次0.2 m L,连续5 d。第22天,麻醉处死裸鼠,检测瘤体积和瘤质量,计算抑瘤率。采用免疫组织化学法、Western blot法及RTQ-PCR法检测肿瘤组织中钙联蛋白(calnexin,CNX)及调控转录因子X盒结合蛋白1(X-box binding protein 1,XBP1)的表达。结果:顺铂注射液组、益气除痰方高剂量组及联合用药组瘤质量及瘤体积较模型组显著降低(P<0.05或P<0.01),且联合用药组显著优于顺铂注射液组(P<0.01)。免疫组织化学法、Western blot法及RTQ-PCR法结果均显示顺铂注射液组、益气除痰方高剂量及联合用药组CNX及XBP1的表达较模型组显著降低(P<0.01),且联合用药组优于顺铂注射液组(P<0.05或P<0.01)。结论:益气除痰方能抑制A549肺癌生长,与顺铂联用能起到增效作用,其机制可能与下调相关分子伴侣蛋白CNX及XBP1的表达而抑制未折叠蛋白反应(unfolded protein response,UPR),从而导致肿瘤细胞凋亡有关。
Objective: To study the inhibition and mechanism on lung cancer A549 cells xenografts in BALB / c nude mice. Methods: 40 BALB / c mice were selected to establish lung cancer xenografts models with human lung adenocarcinoma A549 cells,which were randomized into model group,cisplatin group( 0. 002 g / kg),Yiqi Chutan Formula low-dose group( 3. 0 g / kg),Yiqi Chutan Formula high-dose group( 6. 0 g / kg) and combination group[Yiqi Chutan Formula 6. 0( g / kg) / cisplatin 0. 002( g / kg) ],wiht eight mice in each group. Yiqi Chutan Formula was given once a day with 0. 2 m L from 8th day after modeling,and successive medication for14 days. After given cisplatin with 0. 2 m L by intraperitoneal injection once a day in 17 th day,and modeling for 5 days. The tumor weight and tumor volume were detected. And the tumor inhibitory rate were calculated. The expression of CNX and XBP1 was detected by immunohistochemistry,Western blotting and and real-time quantitative PCR. Results: Compared with the model group,the tumor weight and the tumor volume were lower in cisplatin group,Yiqi Chutan Formula high-dose group and combination group( P 〈0. 01);and the combination group was better than the cisplatin group( P 〈0. 01). The results of immunohistochemistry,Western blotting and real-time quantitative PCR showed that,compared with the model group,the expression of CNX and XBP1 were lower in cisplatin group,Yiqi Chutan Formula high-dose group and combination group( P 〈0. 01),and the combination group was better than the cisplatin group( P 〈0. 05 or P 〈0. 01). Conclusion: Yiqi Chutan Formula can inhibit A549 lung cancer cells in BALB/c nude mice. Combined with chemotherapy drugs,the killing effect on lung cancer can be enhanceed. Its mechanism may be related to down-regulating CNX and XBP1 to inhibit the unfolded protein response to lead to apoptosis.
出处
《中药材》
CAS
CSCD
北大核心
2016年第3期625-629,共5页
Journal of Chinese Medicinal Materials
基金
重庆市科委课题(渝科发计字[2013]22号)