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The Anti-Tumor Effect Of Betulinic Acid On Human Lung Cancer Cell Line A549 And Lewis Lung Cancer In Mice

Posted on:2018-02-20Degree:MasterType:Thesis
Country:ChinaCandidate:Y MinFull Text:PDF
GTID:2334330518962055Subject:Surgery
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Lung cancer is one of the most malignant tumors of mortality and morbidity in recent years, accounting for one third of the world's cancer deaths, the first killer that affects human health. Although the recent progress in lung cancer drug therapy and control of postoperative recurrence has made great progress, but the overall survival rate of patients and quality of life is still not ideal. At present, in order to control the growth and metastasis of lung cancer, the main means is still chemotherapy, but its toxic effects and multi-drug resistance to its further development. Biopharmaceutical preparation has the advantages of small side effects, can improve the overall microenvironment, for the improvement of quality of life of patients and the survivalof the extension has a significant role, it can also effectively reduce the radiotherapy and chemotherapy side effects, to prevent cancer Metastasis recurrence, especially in the treatment of advanced tumors on the outstanding advantages. Therefore, the development of such an efficient, low toxicity of biological agents has become an urgent need for human beings.Betulinic acid can be obtained from eucalyptus, mango white, fenugreek,eucommia, jujube kernel, birch bark and other plants through the extraction method.Due to the low extraction rate, the currently commercially available betulin acid is obtained by chemical synthesis of betulin. In recent years, some progress has been made in the study of betulinic acid at home and abroad. It has been found that it has obvious inhibitory effect on malignant tumors such as malignant nevus neoplasms and hepatocellular carcinoma, but whether it has inhibitory effect on lung cancer and the mechanism of action Not very clear. The aim of this study was to test the antitumor effect of betulinic acid in killing human lung cancer cell line A549 in vitro.OBJECTIVE: To study the antitumor effect of betulinic acid on Lewis lung cancer bearing mice and human lung cancer A549 cell line. The method of extraction and administration of essential oil from Atractylodes macrocephala Koidz was studied with the inhibition rate as the index, and the mechanism of antitumor activity ,For the development of natural anti-tumor drugs to provide a reliable basis.Method:1.Inhibitory effect of betulinic acid on proliferation of human lung cancer A549 cell line in vitro and its mechanism. The cells were divided into four groups: distilled water group, cisplatin group, low dose of betulinic acid group, betulin acid middle dose group and high dose of betulinic acid group. The cell viability of human lung cancer A549 cells was detected by MTT assay. The cell morphology of human lung cancer cell line A549 was detected by flow cytometry. The cell cycle of human lung cancer A549 cell line was detected by enzyme-linked immunosorbent assay (ELISA)The expression of caspase-3 protein in cells.2.The experimental part of the body: betulinic acid on Lewis lung cancer tumor-bearing mice tumor inhibition and its mechanism.The mouse model of Lewis lung cancer was established by mouse axillary inoculation. The mice were randomly divided into three groups: distilled water group,cisplatin group, low dosage group of betulin acid group, middle dose group of betulinic acid group and high dose group of betulinic acid , A total of 5 groups.During the course of administration, the solid tumor volume of the mice was measured and calculated every other day. After 2 weeks of administration, the solid tumor tissue, thymus, spleen, blood were weighed and the tumor growth was calculated The expression of casepase-3 and XIAP protein in the serum of tumor-bearing mice were detected by enzyme-linked immunosorbent assay (ELISA).The expression of casepase-3 and XIAP protein were detected by enzyme-linked immunosorbent assay (ELISA).Results:1. In vitro experimental part:The cell viability was significantly lower in the low dose group of betulinic acid and the high dose group. The cell cycle was blocked by GO / G1 phase, and the expression of caspase- (P <0.05), and the effect of high dose of betulinic acid was the most significant.2.The experimental part of the body:The effect of betulinic acid on the tumor growth factor of Leiws lung cancer mice was significantly higher than that of the low dose group and the heavy dose group. The tumor tissue was found to be necrotic and the tumor cells were scattered.The expression of caspase-3 was increased and the expression of XIAP was decreased in the tumor-bearing mice, which was significantly higher than that in the model group (P <0.05). The effect of the high dose of betulinic acid was the most significant.Conclusion:1 .In vitro experimental part The inhibitory effect of betulinic acid on proliferation of human lung cancer cell line A549 was higher than that of betulinic acid group. The bacillus acid could block the cell cycle of human lung cancer A549 cell in G0/G1 phase and raise the human The expression of caspase-3 in A549 cells was significantly higher than that in the high dose of betulinic acid.2,.The experimental part of the body The betulinic acid could inhibit the expression of caspase-3 in the serum of tumor-bearing mice, and the content of caspase-3 in the tumor tissue of the tumor-bearing mice was significantly higher than that of the betulinic acid group,Down-regulated the expression of XIAP in the serum of tumor-bearing mice, and the effect of high dose of betulinic acid was significant.
Keywords/Search Tags:betulinic acid, human non-small cell lung cancer A549, Lewis lung cancer, antitumor, cell cycle, apoptosis, mechanism, caspase-3, XIAP
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