RÉSUMÉ
Objective:To investigate the effect of heat shock protein 90 (Hsp90) inhibitor PU-H71 combined with X-ray on radioresistant human cervical cancer cells.Methods:The expression levels of Hsp90 gene between cervical cancer tissues and adjacent tissues were analyzed by bioinformatics. Radioresistant cervical cancer cell lines HeLa RR and SiHa RR were obtained by fractional irradiations (2 Gy per fraction, 30 fractions). The cell lines were divided into the control group (treated with dimethyl sulfoxide), irradiation alone group, PU-H71 group (treated with 0.5 μmol/L PU-H71), and PU-H71+irradiation group (irradiation at 24 h after treatment with 0.5 μmol/L PU-H71). Cell survival was detected by clonal formation assay. Immunofluorescence assay was used to detect γH2AX foci at 1, 6, and 24 h after cell treatment. The expression level of Rad51 protein at 1, 2, 6, 12, and 24 h after cell treatment was detected using Western blot. The expression level of phosphorylated DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) was measured at 2 h after cell treatment. Cell apoptosis at 48 h after cell treatment was assessed by flow cytometry. Results:PU-H71 enhanced the sensitivity of radioresistant cervical cancer cells to X-ray. Compared with the irradiation alone group, the radiation sensitization ratios (SER) of HeLa RR and SiHa RR cells at 10% survival were 1.36 and 1.27, and the apoptosis rates were increased by approximately 72.1% and 63.1% in the PU-H71+irradiation group, respectively. PU-H71 delayed the duration of γH2AX foci induced by X-ray, inhibited the phosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), thus preventing non-homologous end joining (NHEJ) repair and delaying homologous recombination repair.Conclusion:PU-H71 increases the radiosensitivity of radioresistant cervical cancer cells by inhibiting the repair pathway of DNA double-strand break, which is expected to be a radiosensitizer to enhance the efficacy of radiotherapy for cervical cancer.
RÉSUMÉ
Objective To systematically review the efficacy and safety of postoperative radiotherapy and postoperative chemotherapy for patients with endometrial cancer,which may give support for clinical proper selection.Methods The randomized controlled trials (RCTs)comparing postoperative radiotherapy with post-operative chemotherapy for patients with endometrial cancer were searched in EMBase,PubMed,Cochrane Library,Chinese Biomedical Literature Data,China National Knowledge Infrastructure,and VIP database from the inception to August 201 5.Two reviewers independently assessed the quality of included studies and extrac-ted data.We analyzed the statistic data using RevMan 5.1 software.Results Three RCTs concluding 1 1 21 patients were included.Meta analysis showed that there were no significant differences between the two groups in five-year survival rate (RR =0.94,95%CI:0.80-1 .1 0,Z =0.77,P =0.440),five-year progression-free survival rate (RR =0.98,95%CI:0.90-1 .07,Z =0.52,P =0.61 0)and recurrence rate (RR =1 .06, 95%CI:0.91 -1 .24,Z =0.75,P =0.450),but there were significant differences between the two groups in grade 3-4 thrombocytopenia (RR =0.1 3,95%CI:0.07-0.27,Z =5.62,P <0.000 01 )and grade 3-4 neu-tropenia (RR =0.01 ,95%CI:0.00-0.03,Z =8.27,P <0.000 01 ).Subgroup analysis showed that there were significant differences between the two groups in five-year survival rate (RR =0.79,95%CI:0.68-0.91 , Z =3.1 5,P =0.002)and five-year progression-free survival rate (RR =0.82,95%CI:0.69-0.97,Z =2.31 ,P =0.020)for patients with Ⅲ-Ⅳ stage endometrial cancer.Conclusion Current evidence indicates that compared with postoperative radiotherapy,postoperative chemotherapy may improve the survival rate for pa-tients with advanced stage endometrial cancer.The long-term curative effects still need to be confirmed by RCTs with high quality and large sample.