Abstract

BackgroundTo evaluate the killing effect of HSV-TK/GCV suicide gene therapy system combined with 60Co radiotherapy on human cervical cancer Hela cell line in vitro and in vivo, and to explore the radiosensitization by HSV-TK/GCV system.MethodsHSV-TK/GCV suicide gene therapy system and 60Co radiotherapy were used separately or in combination on human cervical cancer Hela cell line in vitro and in vivo to compare their effects. Colony formation test and the rate of radiosensitization effect (E/O) were employed to observed the radiosensitization by HSV-TK/GCV system.ResultsHSV-TK/GCV suicide gene therapy system had strong therapeutic effects on Hela cells in vitro and in vivo (the inhibition rates were 45.8% and 39.5%, respectively), moreover, the combined administration of gene therapy and radiotherapy had stronger therapeutic effects in vitro and in vivo (the inhibition rate was 87.5% in vitro, and the inhibition rate was 87.9% in vivo) (P < 0.01). The inhibition rate by radiotherapy alone was 42.4% in vitro and 35.8% in vivo. The sensitivity of combined therapy to radiotherapy increased more than that of therapy alone, the ability of colony formation decreased (P < 0.01). The rate of radiosensitivity effect (E/O) was 3.17(> 1.4), indicating HSV-TK/GCV system could exert a sensitizing effect on 60Co radiotherapy of the transplanted human cervical cancer cell in nude mice.ConclusionHSV-TK/GCV system had radiosensitization. Gene therapy combined with radiotherapy may be a good supplementary method for cervix cancer synthetic treatment.

Highlights

  • To evaluate the killing effect of HSV-TK/GCV suicide gene therapy system combined with 60Co radiotherapy on human cervical cancer Hela cell line in vitro and in vivo, and to explore the radiosensitization by HSV-TK/GCV system

  • Cell growth inhibition On 4th day, inhibition rates of Hela/TK cell growth in the three treatment group were 45.8 ± 7.3%, 42.4 ± 5.6% and 87.5 ± 10.32% respectively, compared with gene treatment group and radiotherapy group, there was a significant difference in combined treatment group (P < 0.01) (See Figure 1)

  • Hela/TK cells apoptosis analyzed by FCMs The percentages of Hela/TK cells apoptosis were analyzed by FCMs on the fluorescence channel as described by Zhang [9]

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Summary

Introduction

To evaluate the killing effect of HSV-TK/GCV suicide gene therapy system combined with 60Co radiotherapy on human cervical cancer Hela cell line in vitro and in vivo, and to explore the radiosensitization by HSV-TK/GCV system. Methods: HSV-TK/GCV suicide gene therapy system and 60Co radiotherapy were used separately or in combination on human cervical cancer Hela cell line in vitro and in vivo to compare their effects. Colony formation test and the rate of radiosensitization effect (E/O) were employed to observed the radiosensitization by HSV-TK/GCV system. More attention is paid to HSV-TK/GCV drug sensitive gene treatment system. Main complications are damage to renal function (40%~60%) and bone marrow inhibition (20%~41%) [1], which greatly influence and limit application scope and therapeutic effect of HSV-TK gene treatment. Radiotherapy is one of the most important clinical means in the treatment of tumor.

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