Font Size: a A A

Effect Of Combined Chemotherapy With Teniposide On Gastric Cancer Cells

Posted on:2005-05-18Degree:MasterType:Thesis
Country:ChinaCandidate:Z F LuoFull Text:PDF
GTID:2144360125457784Subject:Oncology
Abstract/Summary:PDF Full Text Request
Gastric cancer is one of the most common tumors worldwide. Its incidence and mortality rate is No. one in our country. Surgery is the major therapeutic option. However, there being micro metastasizes, a lots of penitents have hazards of relapse and metastasis. Advanced cancer, relapse and metastasis tumor were very common in clinical. Therefore, chemotherapy is becoming more and more important in the therapy of gastric cancer. Gastric cancer was considered to be a relative chemo responsive tumor. There are no standard combination chemotherapeutic protocols for advanced gastric cancer, the response rates of the combination regimens currently available for gastric tumor is 40%~60%. Further improving the effect of managements is an urgent problem to be settled. To improve the effect, a lots of research have been studied, including exploit of new drugs, combined chemotherapy with suitable drugs to increase effect, and so on, and progress have been made continually.DNA topoisomerases are nuclear enzymes, which modify DNA topology, they play an essential role during chromosome replication, transcription, segregation of daughter molecules, DNA-damage-repair; they are also associated with multi-drug resistance and they are involved in the mechanisms of apoptosis of cancer cells. Since the level of topoisomerases expression in tumor is more than normal tissues, inhibition of topoisomerase activity can result in the inhibition of growth of cancer cells. Given this reasons, they have became important anti-neoplastic targets of someanticancer agents. In recent years, topoisomerase inhibitors have commonly used in treatment of many kinds of carcinomas, which have achieved better effect in treatment of lung cancer, colon cancer, ovarian cancer, and so on. Topoisomerases inhibiting anti-neoplastic agents are among the most effective anti-neoplastic drugs currently available for cancer therapy .Teniposide(VM-26) and etoposide(VP-16), semi-synthetic derivatives of podophyllotoxins, were inhibitors of topo II ,approved for a wide variety of tumors .They work through inhibition of topo II , and interfere the reunite of the double strands of DNA, and arrest the cell cycle in Ga/M phase to induce apoptosis of cancer cells. The two drugs commonly used hi treatment of many kinds cancers. Etoposide is a critical component in most chemotherapy regimens for gastric cancer, teniposide is commonly used as therapy for acute lymphocyte leukemia, and neuroblastoma; it is not a component of standard chemotherapy for gastric cancer. Some datum had showed that VM-26 is 10 fold more than VP-16 in killing cancer cells hi vitro. However there are little literature s about VM-26 's basic research on gastric cancer both in internal and overseas, especially no basic research reports have been shown in VM-26 combined other drugs. To design combined therapeutic regimens with better antineoplastic activity and/or less toxicity, to further explore the antineoplastic activity of VM-26, a trial were performed to observed the antineoplasic activity of VM-26 alone and combined with the other drug currently used in chemotherapeutic protocols, to evaluated the value of the regimens containing VM-26. We expect that the results could provide the theoretical basis for clinical medication of gastric tumor.Material and methods: ( 1 ) human gastric cancer cell BGC-823 was chosen as the trial material . ( 2 ) chemotherapeutic drugs included VM-26 , VP-16, 5-fluorouracil(5-FU), cis-Dismine-dichloroplatinum(DDP), Paclitaxol(TAX), (HCPT) . ( 3 ) MTT assay was used to examine suppressive rate of cell growth dealt with various concentration of VM-26, VP-16, TAX, 5-FU, HCPT, DDP single and combined with the other drugs for 48 hour. (4) the development of cell cycle and apoptosis induced by different drugs was examined by flow cytometry at 0,12,24 and48h in smaller concentration alone and in combination. ( 5 ) The protein expression of cell apoptosis associated genes p53and Survivin was examined by immunochemistry in the depent on management group (adding VM-26 2.5...
Keywords/Search Tags:Gastric cancer, Cell cycle, Apoptosis, Chemotherapy.
PDF Full Text Request
Related items