The Study Of Bioactive Peptide HP7 Inhibiting Leukemia Cell Proliferation

Leukemia is a systemic blood disease derived from malignant proliferation of hematopoietic stem cells. It is due to a mass of immature white blood cells infiltrate the body via the blood circulatory system, and cause pathological changes in multiple tissues and organs. Compared with other malignant blood diseases, leukemia have a higher incidence, especially acute leukemia, its mortality rate was ranked first in children and adolescents with malignant tumor. Nowadays, except bone marrow transplantation, there have not yet developed a specific drug to treat leukemia, Clinical chemotherapy drugs always have some problems include drug toxicity, side effects and drug resistance. Therefore, this makes people eager to find a safer, effective methods or drugs to cure leukemia. Small molecule peptide, because of its simple structure and specificity which can have an effect for a particular target without intolerable side effects, is now becoming the key research for leukemia drug treatment.The small molecules heptapeptide, in this topics research, was synthesized by chemical synthesis after screening the amino acid sequence with specific effects through bioinformatics method. Through effectiveness analysis of cells in vitro and animal models in vivo, the HP7 was determined to inhibit leukemic cells proliferation. The results in preliminary vitro study showed that the HP7 had significant inhibitory effect on HL-60 cells at concentration range from 0.01 to 100 μM. When the concentration range of HP7 was between 0.01-10 μM, its inhibition to HL-60 cells dependent on time and dosage. Especially, when its concentration was to be 10 μM, the inhibition rate could achieve up to 59.6% at 72 h, HP7 effect for 72 h’s IC50 was 1.35 μM. When the optimum concentration range was reduced, the best inhibitory concentration was 8 μM, and its inhibition rate was 64.6%. In addition, HP7 was determined to have some inhibitory effects for Hep G2 cells to be 27.65% of inhibition rate. There were no effect to the proliferation of normal liver cells L02, the cell viability were more than 95% in each test group.The result of animal trial in vivo showed that HP7 could prolong survival of EL9611 erythroblastic leukemia mice. And the drug effects was administered intravenously to be superior for intraperitoneal injection. Furthermore, it could prolong the longest survival time of EL9611 mice which was 1.37 days when the concentration of HP7 was 10 mg/kg. This treatment was better than AS2O3 treated group. By further pathologic analysis, we found that HP7 could significantly reduce infiltration from the leukemic cell to EL9611 mice’s liver and spleen.The bioactive peptide HP7 was proved to have excellent results for inhibiting leukemia cells proliferation in vivo and vitro, which supplies a solid experimental basis of developing new medicine for curing leukemia.