沙利度胺联合三氧化二砷腹腔注射对肝癌细胞SMMC7721移植瘤生长的影响及机制  

Effect of Tha combined with AsT on the growth of SMMC7721 Xenografts and its mechanism

作　　者：鲁光平[1] 常仁安[2] 刘春[3] 于志坚[2] 巫荣华[4] 黄华[2] 

机构地区：[1]南通大学附属东台医院肿瘤分院,江苏南通224200 [2]南通大学附属医院 [3]南通大学动物实验中心 [4]江苏省神经再生重点实验室

出　　处：《山东医药》2013年第27期29-32,共4页Shandong Medical Journal

基　　金：盐城市医学科技发展计划项目(YK2011054;YK2012074)

摘　　要：目的观察沙利度胺(Tha)联合三氧化二砷(AsT)对肝癌细胞SMMC7721裸鼠移植瘤生长的影响,并探讨其可能作用机制。方法将35只雄性BALB/c裸鼠随机分为7组各5只,均于颈部皮下接种人肝癌细胞株SMMC7721细胞悬液(密度为5×107/mL)0.2 mL,其后按如下方法处理:高、低剂量Tha组分别腹腔注射Tha 25、2.5 mg/kg,AsT组腹腔注射AsT 2.5 mg/kg,高、低剂量Tha联合AsT组分别同前联合给予Tha、AsT,阳性对照组腹腔注射环磷酰胺(CTX)20 mg/kg,阴性对照组腹腔注射生理盐水20 mL/kg,均连续给药4周。观察各组裸鼠皮下移植瘤体积变化及裸鼠行动、对外界刺激的反应;用药结束后处死裸鼠,取部分瘤组织采用RT-PCR法检测血管内皮生长因子(VEGF)mRNA表达,免疫组化法检测Bax、Caspase-3表达。结果裸鼠移植瘤成瘤率100%,瘤体积在高剂量Tha联合AsT组<低剂量Tha联合AsT组<高剂量Tha组<低剂量Tha组<AsT单药组<阳性对照组<阴性对照组,差异均有统计学意义(P均<0.05);移植瘤组织VEGF mRNA表达变化规律同上;移植瘤组织Bax、Caspase-3表达在高剂量Tha联合AsT组>低剂量Tha联合AsT组>AsT单药组>高剂量Tha组>低剂量Tha组>阳性对照组>阴性对照组,差异均有统计学意义(P均<0.05)。结论 Tha联合AsT对SMMC 7721移植瘤的生长具有显著抑制作用,效果优于两单药;机制分别与通过下调VEGF mRNA表达抑制肿瘤血管生成、上调Bax及Caspase-3蛋白表达促进肿瘤细胞凋亡相关。Objective To observe the effect of thalidomide （Tha） combined with arsenic trioxide （AsT） on the growth of SMMC7721 xenografts and to investigate the possible mechanism. Methods Thirty-five male BALB/c nude mice subcutaneously injected with 0.2 mL cell suspension （5 ×107/mL） of human hepatoma cell line SMMC7721, were ran- domly divided into seven groups, 5 in each： the high dose Tha group （HTha） intraperitoneal injected Tha 25 mg/kg, low dose Tha group （Ltha） intraperitoneal injected Tha 2.5 mg/kg, the AsT group （AsT） intraperitoneal injected AsT 2.5 mg/kg, the HTha ＋ AsT group （ HTha ＋ AsT） intraperitoneal injected Tha 25 mg/kg ＋ AsT 2.5 mg/kg, the LTha ＋ AsT group （ LTha ＋ AsT） intraperitoneal injected Tha 2.5 mg/kg ＋ AsT 2.5 mg/kg, negative control group intraperitoneal in- jected CTX 20 mg,/kg and the positive control group intraperitoneal injected normal saline 20 mL/kg. All groups were trea- ted for 4 weeks. The volume of the xenografts was monitored, the action and reactions of nude mice were also observed. A month later, the mice were sacrificed for partial tumor tissues ; the expression of VEGF mRNA was measured by RT-PCR, the expression of the Bax and caspase-3 was also detected by immunohistochemisty. Results The tumor formation rate was 100% by HE staining. The tumor volume in each group： HTha ＋AsT 〈 LTha ＋AsT 〈 HTha 〈 LTha 〈 AsT 〈 positive control 〈 negative control, the difference was statistically significant （ all P 〈 0.05 ） ; expression of VEGF mRNA in xeno- grafts： HTha ＋ AST 〈 LTha ＋ AST 〈 HTha 〈 Ltha 〈 AsT 〈 positive control 〈 negative control, the difference was sta- tistically significant （ all P 〈 0.05 ） ; the expression of Bax and easpase-3 ： HTha ＋ AsT 〉 LTha ＋ AST 〉 AsT 〉 HTha 〉 LTha 〉 positive control 〉 negative control, the difference was statistically significant （ all P 〈 0.05 ）. Conclusion Tha combined with AsT can significantly inhibit the growth of SMMC7721xenogra

关 键 词：沙利度胺 三氧化二砷 移植瘤 血管内皮生长因子 肝癌细胞 

分 类 号：R735.7[医药卫生—肿瘤] R73-36[医药卫生—临床医学]