| Liver cancer is very popular in China and the number of patients with primary livercancer has reached347000by2000, which accounts for more than50percent in the world.The main therapies for liver cancer are still surgery and chemotherapy, but the first resectionrate of liver cancer is only20%~30%. In this case, searching for better antitumor drugs withlower side effects is still the main direction for cancer research at present.7-chloro-4-oxygengeneration-KuiLin (chloroxoquinoline, hereinafter referred to as chlorine oxygen quinoxalinbrand names: Ann, body easy), is developed independently by Jilin Tonghua MAOAuspicious Pharmaceutical Company. Tumor-bearing mouse experiments showed that,chloroxoquinoline could effectively suppress tumor growth and prolong the life cycle.In order to clarify the mechanism of chloroxoquinoline on tumor suppression, we carriedout the research and focused on the process of cell apoptosis induced by chloroxoquinoline, aswell as the relevant mechanism. We studied the function of chloroxoquinoline in cellapoptosis induction and found the activity of caspase-3signaling pathway was deregulated,which led to higher rate of cell apoptosis. We performed Western-Blot to analysis theactivated form of PARP, which is the downstream substrate of caspase-3. PARP expressionwas increased by chloroxoquinoline with dose dependent relationship. According to theresults of in vitro experiments, we treated the HepG2xenograft tumor with75mg/kg and150mg/kg chloroxoquinoline, and found the size of tumor decreased dramatically compared withthe control group. These results demonstrate that chloroxoquinoline can activate caspase-3signaling pathway and the downstream substrate PARP, and then induce the apoptosis of livercancer HepG2cells, which leads to the suppression of tumor development. Nanomaterial is refers to the three dimensional space at least one dimensional in nanoscale, namely1-100nm, about10-100atoms are arranged closely together in the length, alsoinclude the material composed by them. Since it has particular mechanics, optical, magnetism,thermal and chemical properties, relevant application is developed rapidly, and the frequencyof contacting nanometer materials has increased. But the nanometer material safety evaluationsystem is still in the establishment stage. The existing related national standards, environment,occupational health and safety evaluation standard content mentioned in evaluation method ofnanometer materials safety evaluation are not sure applicable, so exploring a series ofnanometer materials safety evaluation methods is the immediate task.The synthesis of nanometer materials PP80by the China academy of sciences institute ofapplied chemistry is the modified products of commercialized transfection reagentpolyethylene imine (polyethylenimine, PEI). It is a kind of amphiphilic materials through thePEI25k amino trigger Phenylalanine-NCA ring opening. We combined with the practicalapplication of nanometer materials PP80, earnestly studied “the quality control standard forpharmaceutical non-clinical research ","pharmacopoeia of the People’s Republic of China(2005edition)”,” law of the People’s Republic national standards-medical equipment biologyevaluation" and the People’s Republic of China of the chemicals in the standard relatedinspection experimental requirements, and also studied a number of literature. We use2%the rabbit blood cells suspension fluid, according to the laboratory commonly used transfectsystem which is about200μ L physiological saline contains pEGFPC1plasmid4μ g, theratio of nanometer material PP80and pEGFPC1plasmid is0.3:1,0.4:1,0.5:1,0.6:1and0.7:1, respectively. The evaluation of potential hemolysis on nanometer materials PP80showed that the single nanometer material PP80have strong hemolytic, but when the pDNAhave mixed with PP80will no longer hemolytic, so PP80for gene carrier application is safe.We tested whether nanometer materials PP80had a original hot check according to “statepharmacopoeia of the relevant provisions of the pyrogen”, and the results showed that thenanomaterials PP80had no hot original, and it would not cause fever reaction in the body. Inaddition, according to the relevant provisions of national standards about chemical drugtesting, as well as the application concentration of PP80(0.2u g/μ L), we set up0.2ug/μL,1μg/μL and5μg/μL three doses gradient, the use of nanometer materials PP80as skin irritantfor the tests, and the results showed that the nanomaterials PP80don’t have skin irritation. Allthe above results showed that the nanomaterials PP80as a geneticp carrier applied to the bodywill not cause hemolytic, the original heat reaction and related skin stimulation phenomenon. |
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