Isobaric tags for relative and absolute quantitation (iTRAQ) technology was adopted to screen differentially-expressed proteins in the serum that predict the effects of chemoradiotherapy on esophageal squamous cell carcinoma (ESCC). Thus, significantly related proteins can be functionally identified at the cellular level. A total of 60 patients diagnosed with locally advanced and advanced ESCC were recruited and treated with chemoradiotherapy. The iTRAQ technique was used to screen serum differentially expressed proteins associated with chemoradiotherapeutic efficacy. Functional identification of significantly related proteins was performed at the cellular level. Cell proliferation was detected using MTT, clonogenic and fluorescence assays, and apoptosis was assessed using flow cytometry. Transwell and wound-healing assays were used to detect the invasion and migration properties of cancer cells. Proteomics results revealed that prior to chemoradiotherapy, the expression level of integrin-linked kinase (ILK) was significantly upregulated in patients with ESCC, compared with that of the control group [ratio (r)=4.386; P<0.05], and significantly downregulated in the chemoradiotherapy-sensitive group, compared with the chemoradiotherapy-resistant group (r=0.587; P<0.05). At the cellular level, the proliferation rate of cells in the experimental group was significantly inhibited (P<0.05), and the number of cell colonies was decreased (P<0.01), while the number of apoptotic cells was significantly increased (P<0.01). The invasive ability of TE-1 cells in the shILK group was significantly inhibited (P<0.01), and the migration rate was significantly retarded at 8 and 24 h (P<0.01). The present study highlighted the potential value of ILK in predicting the efficacy of chemoradiotherapeutic treatment in patients with ESCC, and that ILK gene-silencing inhibits the progression of ESCC.
Background: To evaluate the role and safety of endostar in cervical cancer by comparing the efficacy and adverse reactions of endostar combined with concurrent chemoradiotherapy in patients with locally advanced cervical carcinoma.Methods: The quality of the included literature was evaluated by searching the database for the comparison of endostar combined with concurrent radiotherapy and chemotherapy in cervical cancer patients; objective response rate (ORR) and disease control rate (DCR) were used as the main outcome indicators, and statistical analysis was performed using RevMan5.3 and State15.3 software.Results: A total of 13 studies were included in this study, including 1057 patients with locally advanced cervical cancer, suggesting that endostar combined with chemoradiotherapy can significantly improve the objective response rate (ORR: odds ratio 3.88, 95% confidence interval 2.77-5.45, P < .00001) and disease control rate (DCR: odds ratio 4.43, 95% confidence interval 2.78-7.04; P < .00001), and there was no significant increase in treatment-related adverse reactions.Conclusions: In this meta-analysis, endostar combined with concurrent chemoradiotherapy significantly improved ORR and DCR in patients with locally advanced cervical cancer without increasing toxicity. However, this study only analyzed the shortterm efficacy of endostar, and its influence on overall survival and progression-free survival needs to be further verified in large randomized controlled trials with long-term follow-up.Abbreviations: CCRT = concurrent chemoradiotherapy, CR = complete response, CI = confidence interval, DCR = disease control rate, NOS = Newcastle-Ottawa Scale, NRCT = non randomized controlled trial, ORR = objective response rate, PDGF = platelet-derived growth factor, PFS = progression-free survival, PRISMA = priority report item for systematic review and metaanalysis, RCT = randomized controlled trial, VEGF = vascular endothelial growth factor.
Purpose. Esophageal squamous cell cancer (ESCC) is a deadly malignant tumor characterized by an overall 5-year survival rate below 20%, with China accounting for approximately 50% of all cases worldwide. Our previous studies have demonstrated that high integrin-linked kinase (ILK) expression plays a key role in development and progression of ESCC both in vitro and in vivo. Here, we employed the drug repurposing approach to identify a novel FDA-approved anticancer inhibitor against ILK-induced tumorigenesis and progression. Methods. We screened the ZINC15 database and predicted the molecular docking ability among FDA-approved and publicly available drugs to ILK and then performed computational docking and visual inspection analyses of the top 10 ranked drugs. Two computer-based virtual screened drugs were evaluated in vitro for their ability to directly bind purified ILK by surface plasmon resonance. Cytotoxicity of the two candidate drugs was validated in vitro using CCK-8 and LDH assays. Results. We initially selected the top 10 compounds, based on their minimum binding energy to the ILK crystal, after molecular docking and subjected them to further screening. Taking the binding energy of −10 kcal/mol as the threshold, we selected two drugs, namely, nilotinib and teniposide, for the wet-lab experiment. Surface plasmon resonance (SPR) revealed that nilotinib and teniposide had equilibrium dissociation constant (KD) values of 6.410E − 6 and 1.793E − 6, respectively, which were lower than 2.643E − 6 observed in ILK-IN-3 used as the positive control. The IC50 values for nilotinib and teniposide in ESCC cell lines were 40 μM and 200–400 nM, respectively. Results of the CCK-8 assay demonstrated that both nilotinib and teniposide significantly inhibited proliferation of cells ( P < 0.01 ). LDH results revealed that both drugs significantly suppressed the rate of cell death ( P < 0.01 ). Conclusion. The drug repositioning procedure can effectively identify new therapeutic tools for ESCC. Our findings suggest that nilotinib and teniposide are efficacious inhibitors of ILK and thus have potential to target ILK-mediated signaling pathways for management of ESCC.
Recent studies have shown that the expression of integrin-linked kinase (ILK) was related to the occurrence, development, and malignant progression of esophageal squamous cell carcinoma (ESCC). However, research on the relationship between ILK and the chemosensitivity of ESCC has to date not been reported. The present study found that ILK was highly expressed in ESCC cell lines, and the overexpression of ILK in ESCC cells reduced the incidence of cell apoptosis and alleviated the cytotoxicity on cells induced by cisplatin (CDDP). Inversely, ILK knockdown increased CDDP-induced apoptosis and had an inhibitive effect on the malignant phenotype of ESCC, including cell proliferation, invasion, and migration. In addition, ILK knockdown in ESCC cells inhibited the expression of beta (β)-catenin and activated the wingless/integrated (Wnt) signaling pathway. Furthermore, cellular MYC (c-MYC) and Cylin D1 were the target genes of the Wnt signaling pathway. Rescue experiments showed that the overexpression of β-catenin reversed a tumor’s inhibition and apoptosis abilities induced by ILK knockdown. In conclusion, ILK potentially reduced the CDDP sensitivity of ESCC cells by influencing the activity of the Wnt/β-catenin signaling pathway.
Objective. Esophageal squamous-cell carcinoma (ESCC) is an aggressive malignant tumor, accounting for more than 90% of esophageal cancers. However, treatments such as surgical resection, radiotherapy, and chemotherapy are unable to achieve ideal clinical outcomes. The purpose of this study was to explore the effects of COQ10B on proliferation, apoptosis, migration, and invasion of esophageal squamous-cell carcinoma (ESCC) cells. Methods. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of COQ10B in ESCC and normal tissues and in ESCC cell lines (KYSE-15 and TE-1). MTT assay and flow cytometry were applied to investigate the effects of COQ10B shRNA lentivirus (LV-shCOQ10B) on ESCC cell proliferation and apoptosis, respectively. The effect of COQ10B silencing on ESCC cell migration and invasion was determined by wound healing assay and transwell invasion assay, respectively. Results. The expression of COQ10B mRNA in ESCC tissues was higher than that in surrounding tissues. The decreased COQ10B level in KYSE-15 and TE-1 cells by LV-shCOQ10B could inhibit cell proliferation, promote cell apoptosis, and reduce the ability of invasion and migration (all P < 0.05 ). Conclusion. COQ10B was highly expressed in human ESCC tissues. COQ10B silencing contributed to the inhibition of proliferation, invasion, and migration of ESCC cells and the promotion of cell apoptosis, suggesting COQ10B may be a potential molecular target for the diagnosis and treatment of ESCC.
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