Abstract
BackgroundKu80 is a DNA repair protein which involves in cell apoptosis and chemoresistance. However, it is unclear whether Ku80 correlates with the efficiency of neoadjuvant chemotherapy in human lung adenocarcinoma, and modulates cisplatin/pemetrexed-induced lung cancer cell apoptosis in vitro.MethodsWe recruited 110 patients with stage IIIA lung adenocarcinoma, who received 2 cycles of neoadjuvant chemotherapy, and their lungs were reevaluated by CT scan. Immunohistochemistry and qRT-PCR was performed to detect the expression level of Ku80. A549 cells were transfected by lentiviral vector containing shRNA and full length cDNA to knockdown or upregulate Ku80 gene expression. CCK8 assay, flow cytometry and Western blot were employed to determine the viability and apoptosis of A549 cells treated with cisplatin combined with pemetrexed.ResultsKu80 expression was detected in 76 patients (69%). There were 38 patients who responded to chemotherapy, where Ku80 was positively expressed in 7 cases (18.4%). Immunohistochemical score of Ku80 protein in the response group (2.079 ± 1.617) to chemotherapy was lower than that in the nonresponse group (5.597 ± 2.114, P < 0.05). Tissue samples from the nonresponse group exhibited higher Ku80 mRNA levels compared to the response group. Ku80 knockdown by shRNA augmented cisplatin/pemetrexed-induced decline in viability, whereas Ku80 overexpression attenuated viability reduction induced by these drugs compared to control A549 cells. Both flow cytometry and Western blot analysis displayed that the apoptotic rate of Ku80 shRNA-transfected A549 cells was significantly increased compared to control cells treated with cisplatin/pemetrexed, which was lowered by Ku80 overexpression.ConclusionKu80 could predict the probability of resistance to neoadjuvant chemotherapy in lung adenocarcinoma, and reduced cisplatin and pemetrexed-induced apoptosis in A549 cells.
Highlights
Ku80 is a DNA repair protein which involves in cell apoptosis and chemoresistance
Patients Lung cancer patients consulted in the Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University from September 2013 to September 2016 were examined by bronchoscopy. 110 patients with pathological diagnosis as lung adenocarcinoma with clinical classification stage IIIA were recruited for this study
Ku80 correlated with resistance to neoadjuvant chemotherapy in patients with lung adenocarcinoma One hundred ten patients of clinical classification were stage IIIA and pathology diagnosed by bronchoscopy examination (Fig. 1)
Summary
Ku80 is a DNA repair protein which involves in cell apoptosis and chemoresistance. It is unclear whether Ku80 correlates with the efficiency of neoadjuvant chemotherapy in human lung adenocarcinoma, and modulates cisplatin/pemetrexed-induced lung cancer cell apoptosis in vitro. When patients are diagnosed as lung cancer, most of them has been at the middlelate stage, according to the tumor-node-metastasis (TNM) classification for non-small cell lung cancer (NSCLC) of UICC in 2009 [2]. Curative surgery could be effective until tumor regresses apparently and ipsilateral mediastinal metastatic lymph nodes disappear after 2 cycles of chemotherapy. When reevaluating the tumor status through contrast Computed Tomography (CT) after 2 cycles of neoadjuvant chemotherapy, we find that only a few patients can obtain ideal efficiency. Finding an indicator to predict the resistance to neoadjuvant chemotherapy would promote our understanding of individual treatment strategy
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