赤魟尾刺提取物的抗肿瘤作用

<正>赤魟Dasyatis akajei(Muller&henle)隶属于软骨鱼纲,下孔总目,鲼形目,魟科,魟属,常栖息于底质为泥沙的深潭中[1-3]。赤魟肉性味甘、咸平,有补气之功效。用其熬油,主治小儿疳积。尾刺研末入药,对治疗胃癌、食道癌、肺癌、乳腺炎、咽喉炎、疟疾、牙痛、魟鱼尾刺刺伤均有一定疗效[4]。赤魟尾刺含有多种毒素,有重要药理作用。涂洪斌等克隆出编码赤魟肿瘤抑制因子IPL的全长cDNA序列[5],并报道了赤魟亲环素A的融合表达、纯化及活性特征[6]。目前,赤魟尾刺的生物活性成分及其相关毒理和药理作用仍不清楚[7]。笔者研究了赤魟尾刺提取物(extracts of caudal spine,ECS)对小鼠可移植性肿瘤生长的影响,现将结果报告如下。     

赤魟尾刺提取物的抗肿瘤作用

赤缸Dasyatis akajei（Muller＆henle）隶属于软骨鱼纲，下孔总目，鲼形目，魟科，魟属，常栖息于底质为泥沙的深潭中。赤魟肉性昧甘、咸平，有补气之功效。用其熬油，主治小儿疳积。尾刺研末入药，对治疗胃癌、食道癌、肺癌、乳腺炎、咽喉炎、疟疾、牙痛、魟鱼尾刺刺伤均有一定疗效。赤魟尾刺含有多种毒素，有重要药理作用。涂洪斌等克隆出编码赤魟肿瘤抑制因子IPL的全长cDNA序列，并报道了赤魟亲环素A的融合表达、纯化及活性特征。     

The antitumor effect of bromophenol derivatives <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">Leathesia nana</Emphasis> extract <Emphasis Type="Italic">in vivo</Emphasis>

To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-(2,3-dibromo-4,5-dihydroxybenzyl)-2,3-dibromo-4,5-dihydroxy benzyl methyl ether (1), (+)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroisobenzofuran (2), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethyl-pyrocatechol (3), 2,2′,3,3′-tetrabromo-4,4′,5,5′-tetrahydroxy-diphenylmethane (4), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (5), 2,2′,3-tribromo-3′,4,4′,5-tetrahydroxy-6′-ethyloxymethyldiphenylmethane (6) were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTT assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Bel7402 and HCT-8. Their inhibitory activity against protein tyrosine kinase (PTK) with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana (EELN) was evaluated on S₁₈₀-bearing mice. All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC₅₀ below 10 μg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4%, respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenol derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer. Supported by the National High Technology Research and Development Program of China (863 Program, No. 2007AA09Z410) and Knowledge Innovation Program of Chinese Academy of Sciences (No. KZCX2-YW-209)