α-双炔失碳酯等对Swarm大鼠软骨肉瘤在小鼠肾囊膜下生长的抑制作用

INHIBITORY EFFECT OF α-ANORDRIN AND OTHER DRUGS ON THE GROWTH OF SWARM RAT CHONDROSARCOMA IMPLANTED INTO SUBRENAL CAPSULES OF MICE

目的 研究双炔失碳酯 (ANO)及其 α异构体 (α-ANO)、三苯氧胺 (TAM)、顺铂 (CDDP)、全反式维甲酸(ATRA )对 Swarm大鼠软骨肉瘤 (SRCS)体内外生长的影响和机制。方法 观察药物 SRCS在小鼠肾囊腺下体内生长的影响 ;von Kossa法观察药物治疗对 SRCS中钙盐沉积的作用 ;用台盼蓝排染法观察了药物对 SRCS细胞体外生长的影响 ;以对硝基苯酚磷酸酯为底物研究药物对 SRCS细胞中碱性磷酸酯酶 (AL Pase)活性的影响 ;用邻甲酚酞络合酮比色法测定 SRCS细胞中的钙含量。结果 几种药物对 SRCS在小鼠肾囊膜下体内生长均有程度不一的抑制作用 ,α- ANO在 2 0 m g/ kg剂量下的生长抑制率为 79.4% ;CDDP、ATRA、TAM、α- ANO和 ANO作用 96 h对 SRCS细胞体外生长的 IC5 0 分别为 0 .45、1.47、115 .2、16 1.7和 2 41.5μmol/L ;α- ANO和 ATRA在体内可引起 SRCS中出现钙盐沉积 ;在体外作用 96 h可使 SRCS细胞中 AL Pase活性和钙含量显著性升高 ;而 CDDP和 TAM无上述现象。结论 α- ANO和 ATRA抑制 SRCS生长与其诱导 SRCS向成骨化方向分化有关 ,提示诱导分化治疗可能为临床治疗软骨肉瘤的新的有效途径。

Objective To study the influence of anordrin (ANO),α-ANO, tamoxifen (TAM),cisplatin (CDDP) and all trans retinoic acid(ATRA) on the growth of Swarm rat chondrosarcoma (SRCS). Methods Effects of drugs on the growth of SRCS implanted into subrenal capsules of mice were studied in vivo. Calcium deposits in SRCS were revealed by von Kossa staining. Trypan blue exclusion method was used for examining the growth condition of SRCS cells cultured in vitro . The alterations of alkaline phosphatase (ALPase) activity of SRCS cells were observed with p nitrophenyl phosphate as substrate. o Cresolphthalein complexone colorimetry was employed to study the calcium content of SRCS cells. Results The tested drugs could inhibit the growth of SRCS implanted into subrenal capsules of mice at different degrees, and α-ANO caused 79.4% inhibition at the dosage 20 mg/kg. The IC 50 of CDDP,ATRA,TAM, α-ANO and ANO for SRCS cells after 96 h treatment wree 0 45, 1 47, 115 2, 161 7 and 241 5 μmol/L respectively. Calcium deposits were observed in SRCS treated by α-ANO and ATRA in vivo . α-ANO and ATRA also induced a significant elevation of ALPase activity and calcium content in SRCS cells in vitro for 96 h treatment. These phenomena were not observed in SRCS treated by CDDP and TAM. Conclusion Inducing SRCS toward differentiation and ossification was involved in the growth inhibition of SRCS caused by α-ANO and ATRA, but not by CDDP and TAM. The differentiation induction may be a new approach for clinical therapy of chondrosarcoma.$$$$