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Experimental Study on Treatment of Human Gastric Cancer Cell with Combination of Docetaxel and FHIT

Author: LiJianHua
Tutor: XuHongWei
School: Shandong University
Course: Internal Medicine
Keywords: Stomach tumor Gene Fragile histidine triad Docetaxel Gene transfection Apoptosis
CLC: R735.2
Type: Master's thesis
Year: 2009
Downloads: 29
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Abstract

Background and Purpose Gastric cancer is one of the common malignant tumors of the human malignant tumors morbidity and mortality in the first ranking in the country, the majority of cases are diagnosed at middle and late, surgical treatment of the 5-year survival rate of only 20% to 30%, the prognosis remains poor. Although in recent years there have been various surgical improvements and chemotherapy, radiotherapy program improvements, but with little success. Surgical removal can not remove all of the tumor cells, and there are the drawbacks of recurrence and metastasis. Chemotherapy in gastric cancer in addition to the very important means of adjuvant therapy to surgery, gastric cancer cell with a chemotherapeutic drug sensitivity is poor and prone to drug resistance. Chemotherapy as a clinical anti-tumor treatment in killing tumor cells while normal cells have a greater damage, which to some extent limit its efficacy. In recent years, research in gene therapy as a fourth treatment of malignant tumors mode been booming, made a series of encouraging results, is expected to become effective adjuvant therapy of surgery, radiotherapy and chemotherapy. In the process of tumorigenesis, oncogene activation, tumor suppressor gene inactivation, mis-repair gene changes played an important role. In order to completely conquer cancer, it has been engaged in the study of tumor gene, which leads to many oncogenes, tumor suppressor genes, mis-repair gene discovery fragile histidine triad (fragile histidine triad, FHIT) is one of them. FHIT gene is found Ohta et al 1996 study of a familial renal cell carcinoma using exon capture methods, and the corresponding cDNA was cloned. Contains major fragile sites FRA3B and subordinate the protein histidine triad (histidine triad, HIT) superfamily, so named. FHIT gene discovered namely intended to be a candidate tumor suppressor gene. Although in the early scholars to its tumor suppressor role questioned, but more and more studies have shown that, FHIT gene is a tumor suppressor gene. FHIT gene and its mechanism of tumor suppressor gene product of the present study is not very clear, FHIT from multiple pathways are likely to play a tumor inhibition. The study found that, FHIT gene expression in gastric cancer is closely related with environmental carcinogenic factors malignant missing and abnormal rate. Scholars the FHIT gene into tumor cells and effectively expressed some malignant phenotype of the tumor cells can be reversed, may also induce apoptosis in tumor cells, so as to achieve the purpose of treatment of cancer or enhance the traditional treatment methods. Another scholar FHIT gene into lung cancer cell lines and expression effectively, to study the impact of chemosensitivity. The chemotherapy drug docetaxel (docetaxel, DOC) gastric cancer clinical research has been in a leading position as a microtubule stabilizer, two clinical trials have shown that single-agent docetaxel first-line or second-line treatment of advanced gastric cancer was 17% - 24%. Based docetaxel better single-agent activity and FHIT gene in gastric carcinogenesis, development and transfer process in the understanding of the role of this study, these two factors intervene in the FHIT gene loss of expression of human gastric cancer cell line MGC-803 explore the expression of exogenous gene FHIT induced apoptosis of gastric cancer cells to docetaxel, to provide a theoretical basis for the combination therapy of gastric cancer genes and chemical drugs, no report. [Methods MTT assay was used to detect different concentrations (1.0,5.0,10,20,40 μg / ml) and at different times (24h, 48h, 72h) under docetaxel inhibition rate of MGC-803 cells and select the optimal concentration and duration of action; liposomes containing exogenous FHIT gene recombinant eukaryotic expression plasmid stably transfected cell lines of gastric cancer (MGC-803); detected by flow cytometry FHIT transfection and DOC separate and combined effects The rate of apoptosis; Western blot detection intervention protein expression of the cleaved-Caspase3 around in [Results] 1. obtain stable expression of the FHIT gene in gastric cancer cells. 2.DOC inhibit gastric cancer cell concentration of 20μg/ml, when the time was 48h most obvious. Apoptosis 3.DOC pRcCMV-FHIT level (65.54%) compared to the negative control group (3.27%), pRcCMV group (3.55%), pRcCMV-FHIT group (13.94%), DOC group (44.13%), DOC pRcCMV (45.29%) was significantly higher, and the difference was statistically significant (P <0.05); 4.DOC pRcCMV-FHIT cells of cleaved-Caspase3 protein expression compared to the other groups significantly enhanced. [Conclusion] FHIT gene expression DOC synergistically to promote apoptosis of gastric cancer cells, which may be both synergistic raised Casepase-3 protein expression.

Experimental Study on Treatment of Human Gastric Cancer Cell with Combination of Docetaxel and FHIT

Abstract

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