α-双炔失碳酯对Swarm大鼠软骨肉瘤的分化诱导作用  

Alpha-Anordrin Induced Differentiation of Swarm Rat Chondrosarcoma

作　　者：马仲才[1] 何庚华[1] 张周[1] 胥彬[1] 

机构地区：[1]中国科学院上海药物研究所,上海200031

出　　处：《癌症》2001年第8期834-839,共6页Chinese Journal of Cancer

基　　金：国家自然科学基金项目No39770864

摘　　要：目的:研究α双炔失碳酯(alphaanordrinαanordrin)对Swarm大鼠软骨肉瘤(swarmratchondrosarcomaSRCS)生长的影响及其作用机制。方法:观察αanordrin和全反式维甲酸(alltransretinoicacidATRA)对SRCS在大鼠体内生长的影响;用MTT法研究药物对细胞增殖的影响;用vonKossa法显示钙盐在组织中的沉积;用免疫组织化学法研究S100蛋白的表达水平;用硝基苯酚磷酸酯显色法检测碱性磷酸酯酶活性;用Fura2/AM荧光法测定细胞内自由钙离子浓度。结果:αanordrin对SRCS在大鼠体内生长有剂量依赖性的抑制作用,在16mg·kg-1时的抑制率为41.2%P<0.05,ATRA在10mg·kg-1剂量下抑制率为70.6%P<0.01。同时,经αanordrin和ATRA治疗后,SRCS中出现明显钙盐沉积;S100蛋白表达水平升高。αanordrin对SRCS细胞体外生长的抑制作用明显弱于ATRA,作用48h后对SRCS细胞生长的IC50分别为161.7μmol/L和1.47μmol/L。αanordrin和ATRA在体外可使SRCS细胞中碱性磷酸酯酶活性和自由钙离子浓度显著性升高。结论:αanordrin对SRCS的生长有明显的抑制作用,这种抑制作用可能与其能够诱导SRCS向成骨化方向分化有关。Objective: To investigate the effect and mechanism of α anordrin on the growth of Swarm rat chondrosarcoma (SRCS). Methods: The growth of SRCS was observed in rats. Von Kossa staining was used to reveal the presence of calcium deposits. The expression level of S 100 protein was determined by immunohistochemistry. The proliferation of SRCS cells in vitro was examined by MTT method. The alkaline phosphatase activity was measured using p nitrophenyl phosphate as the substrate. The cytosolic free Ca2+ concentration (i) was determined by Fura 2/AM method. Results:α anordrin could inhibit the growth of SRCS in vivo in a dose dependent manner and at the dosage of 16 mg·kg-1 with the inhibitory rate of 41.2% (P< 0.05). The growth inhibitory rate induced by all trans retinoic acid (ATRA) at the dosage of 10 mg·kg-1 was 70.6% (P< 0.01). The increases of calcium deposits and expression of S 100 protein in SRCS treated by α anordrin and ATRA were observed. A more pronounced growth inhibition of SRCS cells in vitro was caused by ATRA than by α anordrin, and their IC50 on SRCS cells in vitro by 48 hours treatment were 1.47 μmol/L and 161.7 μmol/L respectively. Significant elevations of the alkaline phosphatase activity and i were also found in SRCS cells treated with α anordrin and ATRA in vitro. Conclusion: The growth of SRCS can be significantly inhibited by α anordrin, which may be related to the differentiation and ossification of SRCS.

关 键 词：大鼠 软骨肉瘤 Α-双炔失碳酯 全反式维甲酸 诱导 分化 

分 类 号：R738.1[医药卫生—肿瘤]