RESUMO
Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.
RESUMO
The poly ADP-ribose polymerase (PARP) is a class of nuclear enzymes highly expressed in eukaryotic cells and plays a key role in DNA damage repair. In recent years, PARP inhibitors have shown great potential in tumor therapy, and several PARP inhibitors have been approved by the FDA for maintenance therapy of a variety of cancers. PARP inhibitors mainly inhibit PARP enzymes and PARP trapping, resulting in the persistence of DNA single strand breaks, which are converted to double strand breaks during DNA replication. Studies have shown that PARP inhibitors not only have a significant anti-tumor effect, but also have a synergistic effect with radiotherapy. This paper reviewed the potential theoretical basis of PARP inhibitor combined with radiotherapy, summarized the recent progress of preclinical and clinical research on PARP inhibitors in tumor radiotherapy, sorted out the urgent problems in this field, and looked into the application prospect of PARP inhibitors in anti-tumor therapy.
RESUMO
Objective: To investigate the possible association between globus pharyngeus and thyroid abnormalities. Methods: Forty six patients with globus pharyngeus and 50 non globus pharyngeus patients were investigated by using 7.5 MHz high resolution thyroid ultrasound. The micro abnormatities in 2 groups were compared. Results: The incidence of thyroid abnormalities in globus pharyngeus group was 58.9%(27/46),and it was significantly higher than that(18.0%,9/50)in non globus pharyngeus group( P
