摘要
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?
Aim: To study the action and mechanism of anordrin (ANO), α-ANO, tamoxifen (TAM), cisplatin (CDDP) and all-trans retinoic acid (ATRA) on the growth of Swarm rat chondrosarcoma (SRCS) in vivo and in vitro. Methods: The growth of SRCS was observed in rats treated by the above drugs. Steedman and Von Kossa staining were used to reveal the pathological alterations. The expression of fibronectin (FN) was determined by immunohistochemical technique before and after treatment. The effect of these drugs on the growth of SRCS cells in vitro was studied by MTT method. The effect of cortisol, estradiol and testosterone alone or combined with drugs on the SRCS cell growth were observed by trypan blue exclusion method. The change of alkaline phosphatase (ALPase) activity in SRCS cells caused by drugs in vitro was studied using p-nitrophenyl phosphate as the substrate. Results: All these drugs could inhibit the growth of SRCS in vivo. CDDP and ATRA showed the strongest inhibitory activity. The growth inhibitory rates of CDDP at the dosage of 1mg/kg and ATRA at the dosage of 10mg/kg were found to be the same as 70.6%(P< 0.01), but ATRA had no obvious side effect. The calcium deposits and the decreased level of FN in SRCS treated by ANO, α-ANO and ATRA were observed. The IC50 of ANO, α-ANO, TAM, ATRA and CDDP on SRCS cells in vitro were 232.2, 153.5, 0.40, 103.8, 1.30 umol/L respectively. Cell proliferation of SRCS in vitro was found to be increased by cortisol, estradiol and testosterone. Such stimulatory effects of cortisol and estradiol were antagonized by α-ANO and TAM ,but not by CDDP and ATRA. ANO, α-ANO and ATRA also caused increase in ALPase activity of SRCS cells in vitro. Conclusion: 1) The main mechanisms of CDDP, TAM and ATRA inhibiting the growth of SRCS were associated with cytotoxicity, antagonism against the proliferation-promoting activity of some hormones and differentiation induction, and α-ANO had both the latter two kinds of activity. 2 )The induction of differentiation and hormone replacement may be two novel ways for clinical treatment of chondrosarcoma
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
1999年第10期771-775,共5页
Chinese Journal of Clinical Oncology
基金
国家自然科学基金!资助 (39320003)
关键词
软骨肉瘤
Α-双炔失碳酯
全反式维甲酸
治疗
Rat chondrosarcoma α-Anordrin All-trans retinoic acid Differentiation Therapy
