芦荟多糖增强顺铂对肺腺癌裸鼠移植瘤生长的抑制作用

Enhancement of Aloe Polysaccharide on Inhibitory Effects of Cisplatin on Growth of Lung Adenocarcinoma in Nude Mice

关键词:  肺肿瘤  芦荟多糖  顺铂  裸鼠移植瘤

Key words:  lung neoplasm  Aloe polysaccharide  cisplatin  xenograft

摘要:

目的 观察芦荟多糖(Aloe polysaccharide，AP)和顺铂(DDP)合用对人肺腺癌A549细胞裸小鼠移植瘤生长的抑制作用，并初步探讨其作用机制。方法 采用A549细胞株建立人肺腺癌裸鼠模型，将35只，♀，成瘤裸小鼠随机分为7组：对照组(生理盐水0.2 mL)；DDP低剂量组(1.0 mg·kg^-1)；DDP高剂量组(5 mg·kg^-1)；AP低剂量组(10 mg·kg^-1)；AP高剂量组(30 mg·kg^-1)；DDP低剂量组+AP低剂量组；DDP低剂量组+AP高剂量组，隔天腹腔注射给药，共8次。于最后1次给药后48 h处死各组小鼠，收集瘤标本行光镜观察，免疫组化检测p53和bcl-2蛋白表达情况。结果 各实验组肿瘤的生长明显受到抑制，瘤质量明显低于对照组(P<0.01)。低、高剂量AP联合用药组较低剂量DDP组抑瘤作用明显增强(P<0.05)，其瘤重抑制率分别为49.34%和82.61%。高剂量AP组与对照组比较，p53和bcl-2的表达均下调，差异具有统计学意义(P<0.05)，联合用药组该调节作用进一步增强。高剂量DDP组出现不良反应，其余各组无明显不良反应。结论 AP能够增强DDP对人肺腺癌A549细胞裸鼠移植瘤生长的抑制作用，其作用机制可能与AP抑制p53和bcl-2的表达有关。

Abstract:

OBJECTIVE To investigate the effects of Aloe polysaccharide (AP) combined with cisplatin(DDP) on the growth of transplanted lung adenocarcinoma in mice and the corresponding mechanism. METHODS The human lung adenocarcinoma mode was established with A549 cell in nude mice. Thirty five female Balb/c-nu mice with lung adenocarcinoma were randomly divided into seven groups: control group; low-dose DDP group (1.0 mg·kg^-1); high-dose DDP group (4 mg·kg^-1); low-dose AP group (10 mg·kg^-1); high-dose AP group(30 m mg·kg^-1); low-dose DDP plus low-dose AP group; low-dose DDP plus high-dose AP group. All the mice were sacrificed at 48 h after the last injection. Subcutaneous tumor was subjected to histological examination. Expressions of p53 and bcl-2 in tumor tissues were detected by immunohistochemistry. RESULTS In every treatment group, tumor growth was suppressed significantly. Compared with control group, intraperitoneal injection of other groups resulted in a significant inhibition of the growth of A549 cells in vivo (P<0.01). The anti-tumor effect of DDP plus AP was significantly enhanced compared with low-dose DDP group(P<0.05), the inhibitory rate was 49.34% and 82.61%, respectively. Compared with control group, expression of both p53 and bcl-2 significantly increased in high-dose AP group (P<0.05), and in DDP plus AP groups it was much more enhanced. High dose DDP group showed some adverse reaction, while other groups did not. CONCLUSION DDP combines with AP can significantly inhibit the growth of transplanted lung adenocarcinoma in mice in vivo, the mechanism is associated with the down-regulation of p53 and bcl-2.