α-双炔失碳酯等对Swarm大鼠软骨肉瘤生长的抑制作用

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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) 和全反式维甲酸(ATRA) 对Swarm 大鼠软骨肉瘤(SRCS) 体内外生长的影响及其机制。方法:观察了ANO 等对SRCS 在大鼠体内生长的影响, 用Steed man 和Von Kossa 法观察了药物作用后SRCS 的病理学改变, 用免疫组织化学技术观察了纤维连接蛋白(FN) 表达的变化;用MTT 方法研究了药物对SRCS 细胞体外生长的影响,用台盼蓝排染法观察了雌二醇、氢化可的松和睾丸酮单独以及与药物合用对SRCS 细胞体外生长的影响; 以对硝基苯酚磷酸酯为底物观察了药物对SRCS 细胞中碱性磷酸酯酶( ALPase) 活性的作用。结果: 几种药物对SRCS 在大鼠体内的生长都有抑制作用,其中CDDP 和ATRA 作用最显著,分别在1mg/kg 和10m g/kg 剂量下抑制率都达到了70 .6 % ( P< 0 .01) ,但后者无明显的毒副作用。经ANO、α- ANO 和ATRA 治疗后的瘤组织出现钙盐沉积,同时FN 表达减少。ANO、α-ANO、TAM 、ATRA 和CDDP 对SRCS 细胞体外生长的IC50 分别为232 .2 、15? Objective: To study the effects of anordine (ANO) and its alpha isomers (α-ANO), tamoxifen (TAM), cisplatin (CDDP) and all-trans retinoic acid (ATRA) on Swarm rat chondrosarcoma (SRCS) ) Effects of in vivo and in vitro growth and their mechanisms. METHODS: The effects of ANO on the growth of SRCS in rats were observed. The pathological changes of SRCS after drug treatment were observed by Steed man and Von Kossa methods. The changes of fibronectin (FN) expression were observed by immunohistochemistry. The effect of drugs on the in vitro growth of SRCS cells was studied by MTT assay. The effects of estradiol, hydrocortisone, and testosterone alone and in combination with drugs on the in vitro growth of SRCS cells were observed by trypan blue exclusion. The effect of the drug on alkaline phosphatase (ALPase) activity in SRCS cells was observed using a phenol phosphate as a substrate. RESULTS: Several drugs had inhibitory effects on the growth of SRCS in rats, among which CDDP and ATRA had the most significant effects, and the inhibition rates reached 70 at the doses of 1 mg/kg and 10 mg/kg, respectively. 6 % (P < 0 .01), but the latter had no obvious toxic side effects. Calcium salt deposition occurred in tumor tissues treated with ANO, α-ANO and ATRA, and FN expression was reduced. The IC50 of in vitro growth of SRCS cells by ANO, α-ANO, TAM, ATRA and CDDP was 232. 2, 15?
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