The Pharmacological Effects Of New Synthetic Drug ZBH-LM-1205on Inhibition Of Colon Cancer Line-sw1116

Colorectal cancer is one of the Western developed countries died reason, in ourcountry the incidence is increasing year by year. More than80million peopleworldwide die of colorectal cancer annually. Mortality rates in the third place of allmalignancies. Surgery is the best treatment for early colon cancer, but for sometumors in patients with recurrent or metastatic, chemotherapy is still the mosteffective choice for the treatment of a type of colon cancer. Can to some extent reducethe mortality rate of patients with colon cancer. Irinotecan hydrochloride which is atopoisomerase1inhibitor, is now widely used in the clinical treatment of colorectalcancer, the drug of choice. However, because the majority of adverse reactions. It iswidely reported, Iraq’s three-dimensional Kang addition to associated with delayeddiarrhea, nausea and vomiting, and cholinergic syndrome side effects, more than75%of patients can cause third degree of bone marrow suppression. In order to improvethe efficacy while minimizing the generation of drug side effects. Therefore, by meansof chemical modification, eventually developed a new class of chemically synthesizeddrugs ZBH-LM-1205. We speculate that a certain extent, these drugs is likely to playa certain effect...Purpose of the experiment:This experiment used nude mice transplanted tumors in vitro and cell cultureexperiments. From the perspective of immunology, molecular biology, histochemistryto investigate the cytotoxicity of these chemicals are synthetic drugs andpharmacodynamic analysis. Briefly explore the research and its mechanism of action.Methods:Vitro experiments: in vitro96-well plates, cultured colon cancer cell lineSW1116. Blank control group, respectively, and a separate medium control group, thecontrol group of the solvent （DMSO）, positive control （CPT） group, the test druggroup a ZBH-LM-1205（concentration）, the target cells in the control group, MTTassay of cell killing activity. And photographed morphologic changes. Flow cytometryto detect cell cycle. Nude mice experiment: to establish nude mouse model. To be successful modeling.Randomly divided into five groups: ZBH-LM-1205treatment group (60mg kg^-1)the CPT11positive control group (60mg kg^-1). SN38positive control group (60mg·kg^-1), saline group, model group. Continuous tumor administered topically for6days. And changes in body weight and tumor size was measured two days. Theobserved inhibitory rate of change and its the animal general state situation.Dislocation mice were sacrificed three days after withdrawal. To take various organsand tumor masses camera. Tumor slices VEGF, and CASPASE3the IHC staining.Western blotting analysis caspase3expressionResult:1: ZBH-LM-1205therapy for colon cancer cell line SW1116activity wasinhibited, compared with the positive control group: the cell survival rate of the groupadministered with the treatment the increase of drug concentration clearly showingconcentration dependent decrease. Them. The concentration of therapeutic drug500umol/L killing activity of59.30%（P <0.05） difference was statisticallysignificant2: cell morphology and cell viability of the therapy group with the increase of theconcentration of the drug show a downward trend. Compared with the control group.The apoptotic signs stove obvious than irinotecan positive group. In aconcentration-dependent increase3: xenograft tumor model uniform molding rate of100%. Administered five days,two days after withdrawal observed tumor fast inhibitory situation, the results showedthat the: ZBH-LM-120treatment group, the average volume of the tumor mass is lessthan the model group （P <0.05）. Tumor blocks the weighing. Model group tumor fastweight （0.35±0.12）. treatment group, tumor weight （0.17±0.05）. The inhibitory rateof52.30%. Compared to the positive control group. The inhibition rate of better thanirinotecan topotecan positive control group （P>0.05）. With compared to SN38positive group is a significant inhibitory effect4: treatment group individual cardiac sarcoplasmic cohesion dark pink dye andindividual myocardial cloudy swelling, individual tubular epithelial cells visible granular degeneration, liver tissue visible individual liver cells eosinophilic change.SN38were observed in the visible fatty degeneration, eosinophilic change ofindividual liver cells, pancreatic exocrine Ministry the the individual cardiacsarcoplasmic cohesion dark pink dye. The model group individual tubular epithelialcells visible particles degeneration exocrine pancreas visible steatosis individual livercells eosinophilic change, part of the cardiac sarcoplasmic cohesion dark pink dye.The rest of all ethnic groups were normalShrink the tumor tissue of the treatment group, visible bleeding and necrosis cpt11group showed hemorrhagic necrosis the SN38group, heavy bleeding and necrosis,and hemorrhagic necrosis rare other groups5: the tumor slice caspase3IHC results show: the treatment group showed positiveexpression （+++） the SN38control group showing a weak positive （+）.6, Tumor slices VEGF IHC results showed that: the treatment group showedstrong positive expression （+++）, irinotecan control group presented a weakexpression （+）.7: the treated mice ALT content of9.21±1.51U, a downward trend in its contentcompared to the control group. Compared with the model group, significantly reducedConclusion:1: ZBH-LM-1205therapy cytotoxic effect on colon cancer cell line SW1116.2: ZBH-LM-1205drugs obvious inhibitory effect on transplanted tumors3: ZBH-LM-1205therapy drug toxic effects on various organs of mice, no damage tothe liver function4: ZBH-LM-1205drugs will also interfere with the activity of tumor cell proliferationand growth effect through the caspase pathway and （or） VEGFR receptor.