蚤休薯蓣皂苷联合顺铂治疗肺腺癌小鼠的疗效及其作用机制研究

摘要

目的：探讨蚤休薯蓣皂苷（RD）联合顺铂治疗肺腺癌小鼠的疗效及其作用机制。方法2015年12月，选取 SPF 级雄性 T739小鼠48只，接种肿瘤细胞4 d 后随机分为对照组、顺铂组、RD 组、顺铂+ RD 组，每组12只。对照组小鼠腹腔注射0.9%氯化钠溶液，顺铂组小鼠接种肿瘤细胞后第5、12、19天腹腔注射顺铂，RD 组小鼠接种肿瘤细胞4 d 后腹腔注射 RD，顺铂+ RD 组小鼠腹腔注射顺铂+ RD。接种肿瘤细胞后第31天处死各组小鼠，比较4组小鼠体质量、肿瘤体积、肿瘤重量、抑瘤率、肺表面转移结节数，血清血管内皮生长因子（VEGF）、基质金属蛋白酶2（MMP-2）水平，瘤组织中缺氧诱导因子-1α（HIF-1α）、血管生成抑制蛋白（ VASH）、碱性成纤维细胞生长因子（b-FGF）表达情况。结果顺铂组、RD 组、顺铂+ RD 组小鼠体质量、肿瘤重量低于对照组，肿瘤体积小于对照组，肺表面转移结节数少于对照组（P <0.05）；顺铂+ RD 组小鼠体质量、肿瘤重量低于顺铂组、RD 组，肿瘤体积小于顺铂组、RD 组，抑瘤率高于顺铂组、RD 组，肺表面转移结节数少于顺铂组、RD 组（P <0.05）。顺铂组、RD 组、顺铂+ RD 组小鼠血清 VEGF、MMP-2水平低于对照组（P <0.05）；顺铂+ RD 组小鼠血清 VEGF、MMP-2水平低于顺铂组、RD 组（P <0.05）。顺铂组、RD 组、顺铂+ RD 组小鼠瘤组织中HIF-1α、VASH、b-FGF表达水平低于对照组（P<0.05）；顺铂+ RD 组小鼠瘤组织中HIF-1α、VASH、b-FGF表达水平低于顺铂组、RD 组（P <0.05）。结论 RD 联合顺铂能有效抑制小鼠肺腺癌细胞生长，降低血清 VEGF、MMP-2水平及肿瘤组织中HIF-1α、VASH、b-FGF的表达。%Objective To explore the curative effect and mechanism of rhizome dioscin combined with cisplatin in treating rats with lung adenocarcinoma. Methods In December 2015,a total of 48 specific pathogen free male T739 mice were selected,after 4 days of inoculation of tumor cells,all of the mice were randomly divided into A group,B group,C group and D group,each of 12 mice. Mice of A group received intraperitoneal injection of 0. 9% sodium chloride injection,mice of B group received intraperitoneal injection of cisplatin after 5 days,12 days and 19 days of inoculation of tumor cells,mice of C group received intraperitoneal injection of rhizome dioscin after 4 days of inoculation of tumor cells,mice of D group received intraperitoneal injection of rhizome dioscin combined with cisplatin. All of the mice were killed after 31 days of inoculation of tumor cells,body mass,tumor volume,tumor weight,tumor inhibition rate,lung surface metastatic nodules number,serum levels of VEGF and MMP-2,expressions of HIF-1α,VASH and b-FGF in tumor tissues were compared among the four groups. Results Body mass and tumor weight of B group,C group and D group were statistically significantly lower than those of A group,tumor volume of B group,C group and D group was statistically significantly smaller than that of A group,respectively,and lung surface metastatic nodules number of B group,C group and D group was statistically significantly less than that of A group, respectively(P < 0. 05);body mass and tumor weight of D group were statistically significantly lower than those of B group and C group,respectively,tumor volume of D group was statistically significantly smaller than that of B group and C group, respectively,tumor inhibition rate of D group was statistically significantly higher than that of B group and C group,respectively, lung surface metastatic nodules number of D group was statistically significantly less than that of B group and C group, respectively(P < 0. 05). Serum levels of VEGF and MMP-2 of B group,C group and D group were statistically significantly lower than those of A group(P < 0. 05);serum levels of VEGF and MMP-2 of D group were statistically significantly lower than those of B group and C group(P < 0. 05). Expressions of HIF-1α,VASH and b-FGF in tumor tissues of B group,C group and D group were statistically significantly lower than those of A group(P < 0. 05);expressions of HIF-1α,VASH and b-FGF in tumor tissues of D group were statistically significantly lower than those of B group and C group( P < 0. 05). Conclusion Rhizome dioscin combined with cisplatin can effectively inhibit the tumor cell proliferation of lung adenocarcinoma in mice, reduce the serum levels of VEGF and MMP-2,down - regulated the expressions of HIF-1α,VASH,b-FGF in tumor tissues.