Advances in studies on the effect of epithelial-mesenchymal transformation on radiotherapy sensitivity of tumors / 中华放射肿瘤学杂志

Radiotherapy is one of the most important methods in the treatment of malignant tumors. However, the decrease of radiosensitivity of tumor cells is the main reason affecting the efficacy of radiotherapy. Epithelial-mesenchymal transition (EMT) is a complex biological process that confers several characteristics necessary for the progression of malignant tumors, such as tumor initiation, aggressiveness, transmissibility, and tolerance to chemotherapy and radiotherapy. In addition, EMT can also be induced by radiation, which endows tumor cells with radiation resistance. Previous studies have shown that inhibition of EMT could enhance the radiosensitivity of tumor cells, but the overall understanding of the molecular mechanisms, key targets and pathways involved are still lacking. In this article, recent studies on the role of EMT in tumor radiation therapy were reviewed, focusing on the signaling pathway, EMT-induced transcription factors, aiming to deepen the understanding of the effect of EMT on the sensitivity of radiotherapy and provide ideas for improving the clinical therapeutic effect of radiotherapy.

Effect of miR-1269a expression on the radiotherapy sensitivity of H460 stem cell like cells / 解放军医学杂志

Objective To investigate the effect of miR-1269a expression on the radiotherapy sensitivity of H460 stem cell-like cells of non-small cell lung cancer. Methods Non-small cell lung cancer H460 cell line was selected for serum-free suspension culture, and CD133 and CD44 positive H460 stem cells were screened by flow cytometry. qRT-PCR was performed to detect the expression levels of miR-30a, miR-148a, miR-148b, miR-152, miR-411, miR-497, miR-598, miR-424, miR-761, miR-1269a, miR-1280 and CD44, CD133 mRNA in H460 stem cell-like cells. The effects of miR-1269a expression on the radiotherapy sensitivity of H460 stem cell-like cells were analyzed using CCK-8 experiments, stem cell pelleting experiments, flow cytometry, and comet experiments. Results The expressions of CD133 and CD44 mRNA increased 1.30±0.03 times and 1.19±0.02 times, respectively, in H460 stem cell-like cells than in H460 cells (P<0.05). The expression level of miR-1269a was the highest in H460 stem cell-like cells, and was higher than that in H460 cells (P<0.05). After transfection of miR-1269a inhibitor and X-ray treatment, the growth inhibition rate of H460 stem cell-like cells increased significantly (72.11%±2.45%), the apoptosis rate reached to 17.70%±0.54%, and the fragmentation of DNA double-strand breaks in cells also increased significantly. After 2 Gy of X-ray radiation, the tail moment was 1.19±0.02 times of that before transfection, implying that transfection of miR-1269a inhibitor significantly increased the sensitivity of H460 stem cell-like cells to radiotherapy (P<0.05). After transfection of pcDNA3.1-SOX7, the effect of X-ray treatment on H460 stem cell-like cells was similar to that of miR-1269a inhibitor transfection. Simultaneous transfection of pcDNA3.1-SOX7 and miR-1269a mimics reversed the inhibitory effect of transfection of pcDNA3.1-SOX7 on the malignant biological behavior of H460 stem cell-like cells. Conclusion Inhibition of miR-1269a may enhance the radiotherapy sensitivity of non-small cell lung cancer, and the mechanism may be caused by up-regulation of SOX7 expression.

Correlation of Survivin gene and UHRF1 gene expressions with sensitivity to cervical cancer in cervical cancer / 西安交通大学学报(医学版)

Objective: To study the expressions of Survivin mRNA and UHRF1 mRNA in cervical cancer tissues and their relationship with radiosensitivity to cervical cancer. Methods We recruited 112 patients with cervical cancer who underwent radical radiotherapy in our hospital. The expression levels of tumor Survivin mRNA and UHRF1 mRNA were detected by RT-PCR. We analyzed the correlation of expression levels of Survivin mRNA and UHRF1 mRNA, as well as clinical characteristics such as age, stage, tumor differentiation and tumor diameter with radiosensitivity. The independent predictors related to radiosensitivity were analyzed by Logistics. Results: After radiotherapy in 112 patients with cervical squamous cell carcinoma, 48 patients received radiotherapy and 64 patients received radiotherapy. Compared with radiosensitivity group, the degree of differentiation was lower and the tumor diameter was larger, and the expression levels of Survivin mRNA and UHRF1 mRNA were higher in the radioresistance group (P0.05), but Univariate and multivariate logistic analysis showed that Survivin mRNA and UHRF1 mRNA expression levels were the independent predictors of radiosensitivity in the cervical cancer patients. Patients with low expressions of Survivin mRNA and UHRF1 mRNA had higher sensitivity to radiotherapy. Conclusion: The expressions of Survivin mRNA and UHRF1 mRNA are negatively correlated with the sensitivity to cervical squamous cell carcinoma. The lower the expression, the higher the sensitivity of radiotherapy.

The role of miRNA?95 in radiosensitivity of cervical cancer cells / 中华放射医学与防护杂志

Objective To detect the expression of miRNA-95 in cervical cancer tissues and cell lines with different radiosensitivity and study the effect of its regulation on radiosensitivity of cervical cancer cells. Methods Real-time PCR was used to detect the expression of miRNA-95 in cervical cancer tissues of 20 patients with radiosensitivity, 20 patients with radiation tolerance, radioresistant cervical cancer cell lines (HeLa, SiHa), and radiosensitive cervical cancer cell lines (Me180). MiRNA-95 mimics (miRNA-95 mimics group ) and miRNA-95 inhibition ( miRNA-95 inhibition group ) were transfected into radioresistant HeLa and SiHa cells by liposome 2000, miRNA-NC was set as control group. CCk-8 assay was used to detect the proliferation of cervical cancer cells irradiated with 60Co γ-rays at 0,2,4,6,8, 10 Gy. After 4 Gy irradiation, cell clonal formation ability was detected by plate monoclonal assay, and cell apoptosis was detected by flow cytometry. Dual luciferase activity assay was used to detect the target gene of miRNA-95 in cervical cancer cells. Nude mice were used to detect the changes of tumor formation ability. Results The expression of miRNA-95 in cervical cancer tissues of patients with radiotherapy tolerance was significantly higher than that of patients with radiotherapy sensitivity ( t =12. 279, P <0. 05 ) . The expressions of miRNA-95 in HeLa and SiHa cells were significantly higher those that of Me180 cells (t = 5.162, 7.114, P < 0.05). When the cells were treated with miRNA-95 inhibition, the expression of miRNA-95 in HeLa and SiHa cell lines was significantly lower than that of microRNA-NC group (t =5. 162, 7. 114, P < 0. 05), the cell proliferation rate decreased significantly ( t =8. 273, 11. 354, 13. 489, 15. 396 and 6. 197, 9. 185, 10. 994, 12. 442, P<0. 05), the cell monoclonal formation rate decreased significantly (t=8. 378, 7. 931, P<0. 05), and the apoptosis rate increased significantly (t=10. 265, 8. 386, P<0. 05). The tumorigenic weight of nude mice in the miRNA95 inhibition group was significantly decreased (t=8. 881, 10. 037, P<0. 05). Conclusions The miRNA-95 had low levels in both radiosensitive cervical cancer tissues and cells. Inhibiting the expression of microRNA-95 can significantly improve the radiosensitivity of cervical cancer cells by targeting SGPP1 gene.

The clinical value of cyclooxygenase-2 expression to predict the sensitivity of neoadjuvant radiotherapy in rectal cancer / 实用医学杂志

Objective To study the expression of cyclooxygenase-2 (COX-2) in colorectal cancer,and its relationship with the sensitivity of rectal cancer neoadjuvant radiotherapy.Methods 102 rectal cancer patients with preoperative radiotherapy were selected from January 2013 to January 2016.The COX-2 expression of samples were detected by immunohistochemical.We analyzed the relationship of tumor and adjacent to carcinoma tissue COX-2 expression,radiation sensitivity and the prognosis of patients.Results 71 cases with radiation sensitivity and 31 radiation resistance cases,radiation sensitive rate was 69.6％.The COX-2 expression in the tumor tissue was significantly higher than adjacent tissue (P ＜ 0.05),radiation sensitive patient proportion with positive and strong positive COX-2 expression was significantly lower than the radiation resistance (P ＜ 0.05).The adjacent to carcinoma tissue's COX-2 positive expression of radiation resistance group proportion was significantly higher than the radiation sensitive group (P ＜ 0.05).The tumor COX-2 positive OR strongly positive (OR:4.21,95％ CI:1.26-7.17),tissue adjacent to carcinoma COX-2 positive (OR:8.15,95％ CI:1.43-38.21) were risk factors for neoadjuvant radiotherapy resistance.The survival analysis showed that tumor tissue COX-2 expression of negative OR weakly positive patients survival significantly extended.Conclusions There were significant correlations between the expression of COX-2,neoadjuvant radiotherapy sensitivity and prognosis in colorectal cancer patients.the joint detection biopsy COX-2 expression in colorectal cancer patients with tumor and cancer adjacent tissues,may screening out patients sensitive to radiation and chemotherapy,which making patient better prognosis.

Correlation of XRCC1 Polymorphism with Radiotherapy Response in Squamous Cell Carcinoma of Cervix / 天津医药

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.

Radiotherapy Response in Microsatellite Instability Related Rectal Cancer

Preoperative radiotherapy may improve the resectability and subsequent local control of rectal cancers. However, the extent of radiation induced regression in these tumours varies widely between individuals. To date no reliable predictive marker of radiation sensitivity in rectal cancer has been identified. At the cellular level, radiation injury initiates a complex molecular network of DNA damage response (DDR) pathways that leads to cell cycle arrest, attempts at re-constituting the damaged DNA and should this fail, then apoptosis. This review presents the details which suggest the roles of DNA mismatch repair proteins, the lack of which define a distinct subset of colorectal cancers with microsatellite instability (MSI), in the DDR pathways. Hence routine assessment of the MSI status in rectal cancers may potentially serve as a predictor of radiotherapy response, thereby improving patient stratification in the administration of this otherwise toxic treatment.

Effects of wild-type INK4a gene on radiosensitivity of lung adenocarcinoma cell line A549 / 第三军医大学学报

Objective To assess the effects of transfection of plasmid pcDNA3.1-p16 containing the wild-type(wt) INK4a gene on the radiotherapy sensitivity of human lung adenocarcinoma cell line A549. Methods Using cationic liposome, the recombinant eukaryotic expression vectors pcDNA3.1-p16 were introduced into A549 cell line and named as A549-p16, in which the gene site INK4a was lost. By RT-PCR, immunocytochemistry and Western blotting after G418 selection, A549 cells stably expressing p16 were obtained. The parental cell and negative control cell with plasmid pcDNA3-LacZ were used as controls.The colony formation rate and 50% inhibition dose(ID_ 50) were measured and analyzed after radiation. Results As compared with the parental cell and negative control cell, re-expression of p16 in A549 induced the cell arrest at G_ 0/G_ 1. The growth rate and the colony formation rate decreased and the ID_ 50 decreased slightly in A549-p16. Conclusion The exogenous introduction of wtINK4a gene into lung adenocarcinoma cells A549 increased the radiosensitivity.