白英总碱联合顺铂对Lewis肺癌移植小鼠肿瘤生长的影响

Effect of total alkaloids from Solanum lyratum Thunb. combined with cisplatin on tumor growth in mice with Lewis lung cancer

目的探讨白英总碱联合顺铂对Lewis肺癌移植小鼠肿瘤生长的抑制作用及与Notch信号通路的关系。方法皮下注射肺腺癌Lewis细胞建立裸鼠皮下移植瘤模型,按照体重将裸鼠随机分为4组:对照组、白英总碱组、顺铂组、联合组,每组10只。白英总碱组予以灌胃白英总碱24mL·kg-1,每日1次;顺铂组予以腹腔注射顺铂2mg·kg-1,2日1次;联合组予以灌胃白英总碱24mL·kg-1+腹腔注射顺铂2mg·kg-1,对照组予以灌胃等体积0.9%NaCl,3组均连续给药14d。每日测量肿瘤体积,计算抑瘤率(TIR);实时荧光定量PCR(RT-PCR)检测小鼠肿瘤组织中Notch信号通路相关蛋白mRNA表达量。结果对照组、白英总碱组、顺铂组和联合组TIR分别为0,(22.36±3.26)%,(35.16±5.21)%,(78.63±6.94)%;Notch1mRNA相对表达量分别为1.06±0.32,0.58±0.15,0.26±0.09,0.09±0.05;Notch3mRNA相对表达量分别为1.08±0.32,0.65±0.13,0.58±0.11,0.05±0.03,Jagged1mRNA相对表达量分别为1.09±0.41,0.48±0.08,0.29±0.07,0.18±0.05,联合组分别与白英总碱组和顺铂组比较,差异均有统计学意义(均P<0.05)。结论白英总碱可明显抑制Lewis肺癌移植小鼠肿瘤生长,联合顺铂使用具有协同增效作用,其机制与下调Notch信号通路蛋白有关。

Objective To investigate the inhibitory effect of total alkaloids from Solanum lyratum Thunb.(SLT-A) combined with chemotherapy drugs on tumor growth in mice with Lewis lung cancer(LLC) and its relationship with Notch signaling pathway. Methods Nude mice were subcutaneously injected with Lewis cells of lung adenocarcinoma to establish a model of subcutaneous transplantation. According to their body weight, the nude mice were randomly divided into 4 groups(with 10 mice in each group):the control group, the SLT-A group, the cisplatin group and the combination therapy group. The SLT-A group was given oral administration of 24 mL·kg-1 of SLT-A once daily, the cisplatin group was given 2 mg·kg-1 of cisplatin by intraperitoneal injection every 2 days, and the combination therapy group was given 24 mL·kg-1 of SLT-A+2 mg·kg-1 of cisplatin. The control group was given equal amount of 0.9% NaCl. All groups were treated for 14 days. Tumor volume was measured daily to calculate the tumor inhibition rate ( TIR),Real-time fluorescent quantitative PCR( RT-PCR) was used to detect the protein mRNA expression of Notch signaling pathway in tumor tissue. Results There were statistically significant differences between the control group and the SLT-A group/the cisplatin group/the combination therapy group in the TIR [0 vs( 22. 36 ± 3. 26)%,( 35. 16 ± 5. 21)%,( 78. 63 ± 6. 94)%],the relative expression of Notch1 mRNA [1. 06 ± 0. 32 vs 0. 58 ± 0. 15,0. 26 ± 0. 09,0. 09 ± 0. 05],the relative expression of Notch3 mRNA [1. 08 ± 0. 32 vs 0. 65 ± 0. 13,0. 58 ± 0. 11,0. 05 ± 0. 03],the relative expression of Jagged1 mRNA [1. 09 ± 0. 41 vs 0. 48 ± 0. 08,0. 29 ± 0. 07,0. 18 ± 0. 05]( P <0. 05). Conclusion SLT-A can inhibit the tumor growth in mice with LLC,which combined with chemotherapy drugs has synergistic effect,the mechanism is related to down-regulation of the expression of Notch signaling pathways proteins.