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Effect Of Photodynamci Therapy And The Joint Application Of Chemotherapeutics In Human Cervical Carcinoma Hela Cells

Posted on:2012-02-19Degree:MasterType:Thesis
Country:ChinaCandidate:Z J WangFull Text:PDF
GTID:2214330338964279Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Cervical carcinoma is a common malignant tumor in women.Many patients are suffering advanced stage carcinoma because of the deficiency of ego health care consciousnesses and the less widespread of early diagnosis methods.In recent years,the onset age tends to be younger.Photodynamic therapy(PDT) with its effectiveness,safety and less side effects can be synergistic,repeatable,and relatively low costs treatment.PDT provides an opportunity for patients who have advanced cancer and refuse treatment with traditional cancer therapy. Cisplatin is considered as the effective drug of cervical cancer treatment and most widely used in clinic.The main reason for failure of chemotherapy is the drug resistance to cancer cells.Topotecan is a broad spectrum anti-neoplastic drug.The combined use with cisplatin is confirmed.How to overcome drug resistance and ease the side effect will be the key to increase 5-year survival rate for cervical cancer.Heme oxygenase(HO) is the rate-limiting enzyme of heme catabolism.The subtype,HO-1 has a close relationship with the occurrence and development of tumor.Restrain the expression of HO-1 can obviously induce the apoptosis of tumor cells.This experiment will study if or not chemotherapy drugs combined with photodynamic therapy enhance the effect of photodynamic therapy to tumors.This study also explores its mechanism.Objective:To study the effect and mechanism of cisplatin and/or topotecan combined with the 5-ALA photodynamic therapy and its apoptosis mechanism in cervical carcinoma Hela cells in vitro.Methods:The Hela cell lines are divided into six groups (control group;PDT only group;cisplatin and topotecan group;cisplatin and PDT group;topotecan and PDT group;cisplatin,topotecan and PDT group).The concentration of 5-ALA is 1mmol/L, the laser intensity is 5J/cm2.The dose of cisplatin is 10mg/L,the dose of topotecan is 0.4mg/L. The dose of cisplatin and topotecan in DDP-PDT group and DDP-TPT-PDT group is 5mg/L and 0.2mg/L. Avoid light incubation,under otherwise identical conditions.MTT assay was used to examine the proliferation effects of the six groups.The apoptosis is examined by the flow cytometry in the five groups(control group;PDT group;DDP-PDT group;TPT-PDT group and DDP-TPT-PDT group).The expressions of HO-1 in PDT group,DDP-PDT group,TPT-PDT group and DDP-TPT-PDT group were detected by immunocytochemistry.The kim method is used to calculate the combination index,the value q.Results:The proliferation of Hela cells in vitro is restrained obviously in the four groups(PDT group;DDP-PDT group;TPT-PDT group;DDP-TPT-PDT group).The four groups remarkably induced apoptosis of Hela cells and inhibited expression of HO-1 in the cell line.The degree of apoptosis caused by the joint application of chemotherapeutics and photodynamic therapy was greater than that caused by photodynamic therapy alone.The expression of HO-1 in cells declined correspondingly. PDT group and DDP-TPT group aren't synergism.Conclusion:The effect to hela cells is obvious in PDT and chemotherapeutics combined with PDT.The effect to Hela cells of chemotherapeutics combined with photodynamic therapy is greater than that of photodynamic therapy only.The mechanism of apoptosis may be related with the suppression of HO-1 gene.It is not apparent synergism in photodynamic therapy and chemotherapeutics.
Keywords/Search Tags:5-aminolevulinic acid, Cisplatin, Topotecan, Photodynaic therapy, Apoptosis, Cervical neoplasms
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