眼镜蛇毒细胞毒素的体内外抗肿瘤活性及毒性比较  

Antitumor Activities (in vitro and in vivo) and Toxicities of Cytotoxin Isoforms Purified from the Venom of Naja atra

作　　者：张明芳[1] 许云禄[2] 

机构地区：[1]福建医科大学生理学与病理生理学系,福州350004 [2]福建医科大学蛇毒研究所,福州350004

出　　处：《福建医科大学学报》2005年第3期243-246,共4页Journal of Fujian Medical University

基　　金：福建省自然科学基金资助项目(C0310026)

摘　　要：目的比较舟山眼镜蛇毒细胞毒素(CTX)Ⅹ～ⅩⅢ(CTXⅩ～ⅩⅢ)的毒性及抗肿瘤活性,筛选低毒高效的CTX。方法以Meier法测定CTX近似半数致死量(LD50);通过描记心电图测定引起大鼠100%死亡的最小剂量(MLD);以磺酰罗丹明B(SRB)法观察CTX对体外培养的Bel7404细胞和HL60细胞的杀伤作用;观察荷U14及艾氏腹水癌(EAC)小鼠腹腔注射(ip)CTXⅫ、ⅩⅢ的效果,测定肿瘤生长抑制率。结果CTXⅩ～ⅩⅢ对小鼠(iv)的近似LD50值分别为(1.16±0.12),(1.80±0.21),(0.75±0.21),(1.85±0.15)mg/kg;MLD为(183±18),(310±26),(224±16),(343±28)μg/kg(P<0.001)。CTX对Bel7404细胞作用24h的IC50分别为:(2.22±0.28),(2.97±0.10),(1.12±0.13),(2.46±0.28)μg/mL;对HL60细胞作用24h的IC50为:(1.97±0.06),(2.61±0.24),(1.61±0.18),(2.40±0.30)μg/mL(P<0.01)。CTXⅫ和ⅩⅢ(ip)对U14实体瘤和EAC腹水癌均有剂量依赖性抑制作用。结论4种CTX中,Ⅹ、Ⅻ毒性较强,Ⅺ次之,ⅩⅢ最弱。CTX对体外培养肿瘤细胞的细胞毒作用强弱顺序为:Ⅻ>Ⅹ>ⅩⅢ>Ⅺ。Ⅻ和ⅩⅢ对小鼠体内接种的U14及EAC的抑制作用是ⅩⅢ>Ⅻ。在4种CTX中,ⅩⅢ的抗肿瘤作用相对较强,毒性最低。Objective To compared the antitumor activities（ in vitro and in vivo） and toxicities of cytotoxin（CTX） isoforms from Naja atra venom in order to find out one high-efficient and low-toxic CTX. Methods Assays of toxieities of CTX based on approximate LD50（ iv ） values in mice by Meier＇ s method and on the minimal lethal dose inducing 100 % death of animals（MLD） were used. The inhibitions of CTX-Ⅹ - ⅩⅢ on cultured Be17404 cells and HL-60 human leukemia cells were observed and the IC50 values were assayed by Sulforhodamine B（SRB） method. The antitumor effects in vivo by administering CTX-Ⅻ and CTX-ⅩⅢ intraperitoneally on uterus cervix cancer U14-bearing mice and on Ehrilieh aseites carcinoma EAC-bearing mice were observed. Results Their LD50 values in mice of CTX- Ⅹ - ⅩⅢ showed to be （1.16 ± 0.12） , （1.80± 0.21）, （0.75±0.21）, （1.85±0.15）mg/kgbodyweightrespectively. The MLD values showed to be （183 ± 18）, （310 ± 26）, （224 ± 16）, （343 ± 28） μg/kg and had significant difference in analysis of variance （P 〈 0. 001）. The IC50（24 h） values for inhibition of Be17404 cell proliferation, in increasing order, were CTX-Ⅻ 〈 Ⅹ 〈 ⅩⅢ 〈 Ⅺ. The IC50（24 h） values for inhibition of HL-60 cell proliferation, in increasing order, were CTX-Ⅻ 〈 Ⅹ 〈 ⅩⅢ 〈 Ⅺ. The antitumor effect of CTX- ⅩⅢ was greater than that of CTX-Ⅻ . Conclusion CTX-ⅩⅢ exhibited the lowest toxicity and more potent antitumor effect among the four CTX.

关 键 词：细胞毒素类 肿瘤细胞 培养的 宫颈肿瘤 癌 Ehrlich瘤 

分 类 号：R73-3[医药卫生—肿瘤]