Study On The Acute Toxicity Of The AHVAC-Ⅰ From Snake Venom In Mice And The Effect Of AHVAC-Ⅰ On Migration Of Grastric Cancer Cell Line SGC-7901

Objective:To evaluate the safety of agkistrodon halys venom antitumor component-I（AHVAC-I）from snake venom in clinical use,the acute toxicity test in mice was conducted.To explore the effecc of AHVAC-I on the migration ability of human gastric cancer cells SGC-7901,so as to provide experimental support for the development and application of AHVAC-I in the treatment of gastric cancer.Methods:Isolation and purification of AHVAC-I was carried out by using DEAE-52 anion exchange.future experimental using.The 120 mice of clean grade were divided into a control group,AHVAC-Ⅰ（1 mg/kg、1.44mg/kg、2.06mg/kg、2.96 mg/kg、4.25 mg/kg）dose groups（n=20）.Using the modified Karber’s method to ascertain the median lethal dose(LD₅₀)and 95%confidence interval.At the end of the day 7,animal survival,biochemistry,profile,and histopathological changes were analyzed.Meanwhile,the influence of AHVAC-I on the migration of gastric cancer cells was expolred through transwell test.Results:Treatment with AHVAC-I caused significantly behavioral changes.The calculated LD₅₀ for AHVAC-I in mice via intraperitoneal injection was 2.585mg/kg and the 95%confidence limit was 2.233～3.069 mg/kg.The blood biochemical parameters showed that alanine aminotransfe（ALT）,aspartate amino-transferase（AST）,blood urea nitrogen（BUN）and creatinine（Cr）were increased significantly in medium（2.06mg/kg）and high dose（2.96 mg/kg）experimental group compared with the control group（P<0.05）.However,no significant difference in liver and kidney function between the control and low groups（1 mg/kg、1.44mg/kg）（P>0.05）.The histopathology showed degeneration in the liver and kidney of the medium（2.06mg/kg）and high dose（2.96 mg/kg）experimental group.While,no histopathology changes in low groups（1 mg/kg、1.44mg/kg）.Transwell experiment demonstrated that after AHVAC-I treatment,the migration ability of SGC-7901 cells decreased.The statistical results of metastaasis rate in the transwerll experiments showed that the number of grastric cancer cells passing through the membrane in the AHVAC-I treament groups were significantly lower than that n the control group,and it was dose-dependent.Coclusion:Liver might be the target organ after treated with medium and high dose AHVAC-I,but low dose AHVAC-I has no obvious acute toxicity to mice.It was innovatively found that AHVAC-I inhibited the migration of SGC-7901.