| OBJECTIVE: Cervical cancer is a common genital tract cancer in women; its treatment includes mainly radical hysterectomy and radiotherapy. Radiotherapy is the mainstay treatment, especially in advanced cervical cancer; but the 5-year survival rate was only 33%～45% treated with radiotherapy; the survival rate of patients can be determined by the responsiveness to radiotherapeutic treatment. Cancers response to ionizing radiation may be explained by differences in cancer cell death-inducing effectors. Multiple genetic changes in the cancer cell may contribute to radioresistance. The factors of the radiosensitivity are the intrinsic radiosensitivity and repair of the radioation damage and so on. The similar proposal was applyed in the cervical cancer with conventional radiotherapy to date. However, there are obvious difference in the radiosensitivity in the individuals, it is of importance to apply more individualized proposal to the different individual. Following the development of technic of molecular biology, it is possible to diagnose disease at the molular level. DNA is the main target of ionizing radiation, many tumor cell lines that have been studied to date undergo apoptosis following DNA damage. Adjuvant radiotherapy is very importent for patients who local-regional relapse and local control. Most people think that the efficacy of this therapeutic modality belong to the individual inherent radiation sensitivity. So the purpose of the experiment is to investigate the radiosensitivities of 3 human cervical cancer cell lines Hela,Siha,Hcc94 and chose two cell lines with different radiosensitivity for microarray analysis. The microarray analysis to differentially expressed between different sensitivity cancers may guide new method to improve the efficacy of radiotherapy. METHODS: Human cervical cancer cells from the Hcc94 (well differentiated squamous cell carcinoma), Siha( adenocarcinoma), Hela (poorly differentiated squamous cell carcinoma). Cells were irradiated with different doses of 6MV X ray dose (0,2,4,6,8,10 Gy). Cervical cancer cell lines can be seen the shape change before and after irradiation.Survival curves were obtained by SigmaPlot software based on the cell colony formation rate. Cell cycle and apoptosis were analyed by flow cytometer after irradiation. Hela and Siha cells were detected by microarray experiments complete 22K human genome oligonucleotide with 21,329 Homo sapiens for changes in gene expression befor and after X-ray irradiate. Using the fold changes ( up and down) of≥2-fold as a standard. Analyzed all of the genes expressed differentially to show the reproducibility of the gene clip analysis, 4 genes were picked at random, and the results will be proved whether consistent with RT-PCR.RESULTS: The cells became round after irradiationin and showed apoptosis comparing with cells befor irradiated.The SF2 values were 0.725,0.581 and 0.391 respectively. Significant difference was found between Hela and Hcc94 cells (P<0.05). The three SF2 value of cervical cancer cells were obtained by the Survival curve. The SF2 of Hela cell is the highest (0.725), Siha is 0.581, and hcc94 cells is the lowest(0.391), the difference was significant in statistics (P <0.05). Before radiation, the Hela cell of the cell cycle distribution has a lower fractions in G2/M phase and the Hcc94 was higher (10.42%VS18.77%,P<0.05).24 hours after irradiatet the cell cycle distribution of G2/M phases fractions in Hela compared with Hcc94 was 42.9%VS30.95% (P<0.05). 314 and 111 genes that showed≥2-fold difference were obtained by analyzed in Hela and Hcc94 respectively. Finally, 55 genes showing differences more than the average value between the two cells were designated as radiosensitivity-related genes. The RT-PCR results of the 4 genes selected randomly was consistent with the gene clip.CONCLUSION: The radiosensitivity of Hela cell is the lowest, and the Hcc94 is the highest. So we detect the two cell lines with different radiosensitivity by microarray. By analysis we obtained differentially expressed genes including DNA-repair, cell cycle, signal transduction, and apoptosis. Radiosensitivity of cervical cancer with the expressed genes screening at last are closely related. The genes upregulated significantly in Hela ,the radiation resistance cells, will provide a new targets and methods to radiation therapy.
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