皖南蝮蛇毒抑瘤组分I对人胃癌细胞SGC-7901荷瘤鼠体内抑制作用的研究

目的:研究皖南蝮蛇毒抑瘤组分I(Agkistrodon halys venom antitumor component I,AHVAC-I)对人胃癌细胞SGC-7901荷瘤鼠的体内抑制作用及瘤细胞增殖活性变化,并初步探讨其作用机制。方法: 取生长状态良好的浓度为1×10⁷个/mL的SGC-7901人胃癌细胞悬液 0.1 mL 接种于裸小鼠右侧腋窝皮下,待其成瘤后随机分为模型组、紫杉醇阳性对照组、AHVAC-I高、中、低剂量组,隔日连续给药5次,定期观察肿瘤生长情况,测量肿瘤体积,绘制肿瘤生长曲线并计算抑瘤率,HE染色观察瘤体形态学变化,免疫组化SP法检测Ki-67增殖指数,原位末端标记技术(TUNEL)法检测细胞凋亡指数。结果: AHVAC-I在 1.0 mg/kg 剂量时对SGC-7901细胞有抑制作用,抑瘤率达 42.2%;在 3.0 mg/kg 剂量时有显著抑制作用,抑瘤率达 78.5%。实验组肿瘤内Ki-67阳性细胞数量下降,凋亡细胞明显增多。结论:AHVAC-I能明显抑制裸鼠体内SGC-7901人胃癌细胞的生长,其作用机制可能与诱导胃癌细胞发生凋亡及抑制肿瘤细胞增殖有关。

In vivo tumor-inhibitory effects of Agkistrodon halys venom antitumor component I on tumor-bearing mice with human gastric cancer cell SGC-7901

AIM: To investigate the in vivo tumor-inhibitory effects of snake venom antitumor component I(AHVAC-I) from Agkistrodon halys living in south Anhui province on the tumor-bearing mice with human gastric cancer cell SGC-7901 and activities of the cell proliferation as well as its mechanisms.METHODS: Cell suspension of 0.1 mL was obtained from the well-grown cell SGC-7901 by cell count of 1×10⁷/mL and incubated subcutaneously into the nude mice via right axillary fossa. After tumor formation, the mice were randomized into groups of model controls, positive paclitaxiel controls, AHVAC-I of low, medium and low dosage in which the animals were managed with AHVAC-I every other day for 5 consecutive times. The tumor growth and its sizes were observed and measured for mapping the growth curve and calculating the inhibitory rate. HE staining was performed to examine the morphologic change of tumors, and streptavidin-peroxidase (SP) immunohistochemical technique was used to detect the proliferation index of Ki-67 and TUNEL method was for examination of the apoptotic index.RESULTS:AHVAC-I at dose of 1.0 mg/kg produced inhibitory effects on SGC-7901 with inhibition rate of 42.2%, and inhibitory effects were significant at dose of 3.0 mg/kg with a rate of 78.5%. Ki-67 protein was reduced in the positive cells of treatment groups, leading to increased apoptosis of tumor cells.CONCLUSION: AHVAC-I can effectively inhibit the in vivo growth of gastric cell SGC-7901 in nude mice, and the possible mechanisms may be associated with the induced apoptosis and suppressed proliferation of the gastric tumor cells.