[Aspirin inhibits cell stemness of esophageal cancer by downregulation of chemokine CCL2].

Objective: To investigate the effect of tumor-associated macrophages on the stemness of esophageal cancer cells and the potential mechanism of antiproliferative effects of aspirin (ASA). Methods: The effects of aspirin on the stemness characteristics of KYSE-450 cells and KYSE-450 cells co-cultured with M2 macrophages (KYSE-450+ M2) were performed using spheroid formation assay. After treatment with aspirin, the expression of different chemokines, the core pluripotency gene Nanog and the stem cell marker CD90 in different cell groups were determined by real-time quantitative PCR, flow cytometry and Western blot. Results: The number of spheres formed in the ASA and KYSE-450+ M2 cell groups were 7.00±1.23 and 34.33±2.33, respectively, showing statistically significant difference compared with that of control group (14.50±2.33, all P<0.05). The number of spheres in KYSE-450+ M2+ ASA cell group were 20.67±2.33, which was significantly lower than that of KYSE-450+ M2 group (P<0.05). The expression levels of Nanog gene in control and ASA groups were 1.00 and 0.50±0.10, respectively, and the difference was statistically significant (P<0.05). Moreover, the expression of Nanog gene in cells of KYSE-450+ M2 group and M2+ KYSE-450+ ASA group was 1.74±0.13 and 1.43±0.05, showing statistically significant difference (P<0.05). When chemokine CCL2 was knocked down, the levels of Nanog gene in M2+ shCCL2-KYSE450+ ASA group and M2+ shCCL2-KYSE450 group were decreased to 1.22±0.11 and 1.17±0.08, respectively, and there was no statistically significant difference between them (P=0.69). Flow cytometry analyses showed that the expression levels of CD90 in control and ASA cells were (2.93±0.52)% and (1.30±0.17)%, respectively, and the difference was statistically significant (P<0.05). Moreover, the expression levels of CD90 in M2+ shCCL2-KYSE450 cells and M2+ shCCL2-KYSE450+ ASA cells were (4.07±0.12)% and (4.73±0.38)%, respectively, showing no statistically significant difference (P=0.17). Conclusions: Tumor-associated macrophages enhances the stemness of esophageal cancer cells, whereas aspirin attenuates the stemness by suppressing the expression of CCL2. Aspirin plays an anti-tumor effect in esophageal cancer cells.

Association between the c.910A>G genetic variant of the XRCC1 gene and susceptibility to esophageal cancer in the Chinese Han population.

Esophageal cancer (EC) is a common malignancy worldwide. The X-ray repair cross-complementing 1 gene (XRCC1) is one of the most important candidate genes for influencing susceptibility to EC. This study aimed to investigate the effect of XRCC1 genetic variants on susceptibility to EC. A total of 383 EC patients (males: 239, females: 144, mean age: 56.62) and 387 cancer-free controls (males: 251, females: 136, mean age: 58.23) were enrolled in this study. The c.910A>G genetic variant of the XRCC1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. The allele and genotype frequencies indicated statistical differences between EC patients and cancer-free controls. The c.910A>G genetic variant was statistically associated with increased susceptibility to EC [GG vs AA: odds ratio (OR)=1.79, 95% confidence interval (CI)=1.12-2.86, P=0.014; GG vs AG/AA: OR=1.76, 95%CI=1.13-2.75, P=0.013; G vs A: OR=1.25, 95%CI=1.01-1.55, P=0.041]. The allele G and genotype GG could contribute to the increased susceptibility to EC. Our findings suggest that the c.910A>G genetic variant is associated with susceptibility to EC in the Chinese Han population, and might be used as a molecular marker for detecting susceptibility to EC.

Association between the c.910A>G genetic variant of the XRCC1 gene and susceptibility to esophageal cancer in the Chinese Han population

Esophageal cancer (EC) is a common malignancy worldwide. The X-ray repair cross-complementing 1 gene (XRCC1) is one of the most important candidate genes for influencing susceptibility to EC. This study aimed to investigate the effect of XRCC1 genetic variants on susceptibility to EC. A total of 383 EC patients (males: 239, females: 144, mean age: 56.62) and 387 cancer-free controls (males: 251, females: 136, mean age: 58.23) were enrolled in this study. The c.910A>G genetic variant of the XRCC1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. The allele and genotype frequencies indicated statistical differences between EC patients and cancer-free controls. The c.910A>G genetic variant was statistically associated with increased susceptibility to EC [GG vs AA: odds ratio (OR)=1.79, 95% confidence interval (CI)=1.12-2.86, P=0.014; GG vs AG/AA: OR=1.76, 95%CI=1.13-2.75, P=0.013; G vs A: OR=1.25, 95%CI=1.01-1.55, P=0.041]. The allele G and genotype GG could contribute to the increased susceptibility to EC. Our findings suggest that the c.910A>G genetic variant is associated with susceptibility to EC in the Chinese Han population, and might be used as a molecular marker for detecting susceptibility to EC.