舟山眼镜蛇毒及其有效组分体内外抑瘤的作用

目的：观察蛇毒（SV）及其有效组分体内外的抗癌活性，为SV抗肿瘤新药的开发提供实验依据。方法：采用四甲基偶氮唑盐比色法（MTT法）筛查不同浓度（5—20mg／mL）SV及其7种分离组分对人结肠癌细胞株（HCT-8）、人肝癌细胞株（Bel-7402）、人口腔上皮癌细胞株（KB）、人乳腺癌细胞株（MCF-7）的影响；并用小鼠肝癌（H22）动物移植瘤作为实验动物模型，进一步观察SV及其组分Ⅳ（0．01-0．03mg／kg）对瘤重、脾重、外周血白细胞和体质量的影响。结果：SV、Ⅲ2和Ⅳ的肿瘤抑制作用较为明显，三者的浓度在20μg／mL时，对HCT-8、Bel-7402、KB以及MCF-7具有非常显著的抑制作用，对HCT-8的抑制率分别为84．37％、79．39％和85．78％；对Bel-7402的抑制率分别为89．64％、88．13％和92．08％；对KB的抑制率分别为90．08％、91．30％和93．93％；对MCF-7的抑制率分别为89．88％、89．49％和92．33％。腹腔注射10d后，组分Ⅳ对H22有明显的抑制作用，SV组分Ⅳ3个浓度组的瘤重分别为（0．81±0．20）g、（0．70±0．18）g、（0．61±0．17）g，均明显低于对照组瘤重（1．19±0．21）g，P〈0．05]，肿瘤生长抑制率（IR）分别为31．93％、41．17％和48．73％。Ⅳ各剂量组小鼠脾脏指数较对照组增加，白细胞数与对照组相比无明显变化。结论：SV及其7种分离组分均能有效抑制4种人肿瘤细胞株（HCT-8、Bel-7402、KB及MCF-7）的生长，不同的SV分离组分对同一肿瘤细胞抑制作用有差异；不同肿瘤细胞对同一SV分离组分的反应性也不同。SV分离组分Ⅳ对动物移植性肿瘤小鼠肝癌H22有良好的实验疗效。

Tumor-inhibitory activities of the snake venom and its fractionated components from Naja atra Cantor in vivo and in vitro

Objective： To study the tumor-inhibitory activities of snake venom （ SV ） and its fractionated components in vitro and in vivo, and to provide laboratory evidences for developing new anti-cancer preparations of snake venom. Methods： MTT method was used to evaluate the effects of SV （ 5 - 20 mg/mL） and 7 types of its fractionated components on HCT-8, Bel-7402, KB and MCF-7. In hepatoma H22 bearing mice as experimental animal models,the effects of SV and its component Ⅳ（0. 01 - 0.03 mg/kg） on tumor weight, spleen weight, peripheral WBC counts and body weight were evaluated. Results： SV and several of its fractions （ Ⅲ2 and Ⅳ ） showed significant tumor inhibitory activities on HCT-8, Bel-7402, KB and MCF-7 cells. At a level of 20 μg/mL, The inhibition rates（ IR% s） by SV, Ⅲ2 and Ⅳ components were 84.37% ,79.39% and 85.78% ,respectively, in HCT-8 cells; 89. 64% , 88. 13% and 92.08% , respectively, in Bel-7402 cells; 90. 08% , 91. 30% and 93.93 % ,respectively,in KB cells ; 89.88%, 89.49% and 92.33 %, respectively, in MCF-7 ceils. On day 10 after intraperitoneal injection, the SV component IV showed significant inhibition of H22 cells in tumor-bearing mice, as reflected by lower tumor weights （0.81 ± 0.20） g, （0.70 ± 0. 18 ） g and （0.61 ± 0. 17 ） g ] in three groups on different doses of SV-IV compared with control group （1.19 ± 0.21 ）g; P 〈 0.051. In these groups,the IR% was 31.93% ,41.17% and 48.73% ,respectively. Compared with the control group,the SV-IV treated mice showed increased spleen indexes but unchanged WBC counts. Conclusion： Effective growth inhibition in four types of human tumor cells （ HCT-8, Bel-7402, KB, MCF-7 ） was achieved with SV and its 7 fractionated components. The tumor inhibitory activity on a given type of these tumor cells may vary with different SV fractions, and vice versa. Favorable outcome of tumor inhibition in experimental tumor-bearing mice was noted with the fractionated component Ⅳ of snake venom.