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Study On The Inhibition Mechanism Of Shenzhu Capsules On The Occurency Of Spleen-deficient Gastric Cancer By Mitochondrial Pathway Of Cell Apoptosis

Posted on:2012-02-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:H AoFull Text:PDF
GTID:1114330335477625Subject:Pharmacy
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Aims:It is of great social and econimical importance to study and explore the medicine which inhibit the occurency of gastric cancer. The previous study showed the fifth category new medicine Shenzhu Capsules could treat precancerous lesions of gastric cancer and gastric cancer, but the mechanism remained unclear. The study on the inhabition mechanism of Shenzhu Caspsules on the occurency of spleen-deficient gastric cancer by the mitochondrial pathway of apoptosis will provide an example for the studies on the compounded prescription of TCM.Methods:MTT was used to study whether Shenzhu Capsules could inhibit the growing of gastric cancer cell line; the direct observation and the Giemsa's staining was used to study the general effect of Shenzhu Capsules on MKN45 cell line; the electron microscope technique was applied to study the effect of Shenzhu Capsules on the microstrucure of MKN45; the induced spleen-deficient gastric cancer mice model was replicated;the weight, number of spontaneous activity in 5 minutes, and the spleen-deficient manifestation such as little dry stool, abdominal distension, raised hair,squinting,positive pulling-tail reflection were observed after 30d administration of Shenzhu Capsules to the induced spleen-deficient mice model;the HE staining was used to study whether Shenzhu Capsules inhibited the occurance of spleen-deficient gastric cancer; the TUNEL method was used to study the effect of Shenzhu Capsules on the apoptosis index of the induced spleen-deficient mice model; the immunohistochemistry method was used to study the effects of Shenzhu Capsules on the indexes of the induced spleen-deficient mice model including CEA,Caspase-3,Caspase-9,Bax,Bcl2,CytC and P53.Results:The result of MTT showed after 24h and 48h action of Shenzhu Capsules,the OD values of MKN45 was lower;the Giemsa's staining showed that after 24h action of Shenzhu Capsules MKN45 turned round and small and the apoptotic bodies generated. The result of the electron microscope technique showed clustered chromosomes, integrity membrane, swelling mitochondria and increased intracytoplasmic vacuoles in MKN45; after 30d administration of Shenzhu Capsules to the induced spleen-deficient mice model, the HE staining showed the spleen-deficient manifestation was lessened in the model, the TUNEL method showed the apoptosis index increased,and the immunohistochemistry method showed the expression of CytC,Bax,P53,Caspase-3 and Caspase-9 was strengthened and the expression of CEA and Bcl2 was lessened.Conclusions:Shenzhu capsules could inhibit the growth of the gastric cancer cell line, the occurance and development of gastric cancer. The mitochondrial pathway of apoptosis is of great importance accounting for the mechanism.The main way may be that Shenzhu Capsules strengthened expression of P53 and Bax, lessened expression of Bcl2 and increased Caspase-9 which induces the activation of Caspase-3 in the downstream,and lead to cell apoptosis ultimately.
Keywords/Search Tags:Shenzhu Capsules, mitochondrial pathway, spleen-deficient gastric cancer, cell apoptosis
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