ABSTRACT
Objective To investigate the characteristics of radiation resistance of cervical cancer cells,and to explore the mechanism of tumor recurrence and migration.Methods Cervical cancer cells (Siha) were fractionally irradiated to get radioresistant subpopulation.CD44 +/CD24 + Siha cells were sorted with a flow cytometry.Colony-formation tests and tumor xenografts tests were used to evaluate the " stemness" of resistant cells.Stem cell markers were studied using fluorescence-activated cell sorting analyses.Migration and invasiveness were assessed by a Transwell test.Gene and protein expressions were determined by RT-PCR and immunoblotting assay,respectively.Results Radiation-resistant Siha cells and CD44 +/CD24 + Siha cells expressed more antiapoptotic protein Bcl-2(t =205.26,198.17,P ＜0.05),apoptosis-inhibitory protein Survivin (t =896.62,765.34,P ＜ 0.05) and stem cell markers of OCT-4 and ABCG2 (t =92.13,81.26,220.45,216.32,P ＜0.05).They were more tumorigenic in vitro and in vivo,showed phenotypic and molecular changes of EMT,and had higher abilities of invasion and migration.Conclusions The radioresistant cervical cancer cells and CD44 +/CD24 + cervical cancer cells are similar to CSCs and undergo EMT,suggesting that radiation resistance-induced EMT is linked to the generation of CSCs.
ABSTRACT
Objective To investigate the correlation of XRCC1 Arg194Trp Arg399Gln Single nucleotide polymor-phism (SNP) with radiotherapy response of squamous cell carcinoma of cervix. Methods Patients with exogenous type cer-vical squamous cell carcinoma confirmed by histopathology were selected for our study. These include:patients in stageⅠ(4 cases), patients in stageⅡ(36 cases), patients in stageⅢ(30 cases), patients in stageⅣ (3 cases). There are 30 patients with tumor diameter less than 4 cm and 43 patients with tumor diameter over 4 cm in our test. There are 36 cases with dose point A less than 80 Gy and 37 cases with dose point A over 80 Gy . Radiotherapy outcomes showed 47 cases of complete re-mission and 26 cases of part remission. Polymorphisms Arg194Trp, Arg399Gln of XRCC1 gene in 73 cervical cancer pa-tients were analyzed by mismatch amplification polymerase chain reaction (MAMA-PCR). Results Arg/Arg, Arg/Trp, TrP/Trp of Arg194Trp genotype distribution were 31 (42.5%), 37 (50.7%), 5 (6.8%) respectively. Arg/Arg, Arg/Gln, Gln/Gln of Arg399Gln distribution were 6 (35.6%), 39 (53.4%), 8 (11.0%) respectively. The response to radiotherapy was not statistical-ly significant in three genotypes, Arg/Arg, Arg/Trp, TrP/Trp of XRCC1 at codon 194(P>0.05). Neither was XRCC1 at codon 399. Multivariate analysis showed that late clinical stage was a risk factor of part remission. Conclusion SNP of XRCC1 gene at codon 194 and codon 399 could not predict clinical response of patients with squamous cell carcinoma of cervix to ra-diotherapy. The patients with advanced cervical cancer had poor response to radiotherapy.