The generation and development of esophageal adenocarcinoma (EAC) are correlated with neuroimmunological factors. The aim of this study was to observe the effectiveness of the neurotransmitter arachidonic acid (AA) on two EAC cell lines, OE19 and SK-GT-4, as well as three isolated tumor-infiltrating lymphocytes (TIL1, 2 and 3). C-X-C chemokine receptor type 4 (CXCR-4) and tumor necrosis factor receptor 1 (TNFR1) expression, cell migration, necrosis, cytokine secretion and cytotoxicity of TILs were investigated. AA dose-dependently increased the migration of all cells. However, AA did not increase the percentage of cell death of the three TILs in the presence of a necrosis-inducing agent. AA dose-dependently increased the cytotoxicity of the three γδT cell-enriched TILs compared with the OE19 and SK-GT-4 cell lines. AA also dose-dependently increased the secretion of interferon-γ (IFN-γ) and TNF-β in TIL1 and 2. However, the cytokine secretion and cytotoxicity activity of TIL3 and γδT cell-enriched TIL3 were the lowest. Furthermore, the percentage of CD4+forkhead box p3 (Foxp3)+ regulatory T cells in TIL3 was the highest. The effect of AA on tumor cells and TILs is different. The degree of malignancy of the tumor and the ratio of regulatory T cells may be the main factors determining the function of AA.

SMC1A (structural maintenance of chromosomes 1A), which encodes a structural subunit of the cohesin protein complex, is necessary for the process of sister chromatid cohesion during the cell cycle. Mutation and deregulation of SMC1A are highly relevant to diverse human diseases, including Cornelia de Lange syndrome and malignant carcinomas. In order to further investigate the role of SMC1A in the oncogenesis of lung cancer, SMC1A-specific short hairpin RNA (shRNA)-expressing lentivirus (Lv-shSMC1A) was constructed and used to infect A549 and H1299 cells. SMC1A mRNA and protein expression levels were downregulated in A549 and H1299 cells as demonstrated by real-time PCR and western blot assays. We found that SMC1A inhibition resulted in significantly impaired proliferation and colony formation as well as reduced invasiveness of tumor cells. Notably, Lv-shSMC1A-infected cancer cells exhibited a greater proportion of cells in the G0/G1 phase, but a lower proportion of S phase cells, compared to the parent or Lv-shCon infected cancer cells. Moreover, a greater proportion of sub-G1 apoptotic cells was observed in Lv-shSMC1A-infected cells. These results suggest that SMC1A is a novel proliferation regulator that promotes the growth of lung cancer cells, and that down-regulation of SMC1A expression induces growth suppression of A549 and H1299 cells via G1/S cell cycle phase arrest and apoptosis pathways. Therefore, SMC1A may serve as a new molecular target for lung cancer therapy.

Chemotherapy damages the intestinal mucosa, causing adverse gastrointestinal reactions. Clostridium butyricum (C. butyricum) reduces the incidence of diarrhea in digestive diseases, including inflammatory bowel disease. Therefore, the aim of the present study was to investigate the role of C. butyricum in patients undergoing chemotherapy. A total of 41 participants with lung cancer were enrolled, and divided into the C. butyricum (CB) or placebo group using 1:1 randomization to obtain 20 CB and 21 placebo participants. On the first and last day of the 3-week intervention, blood and stool samples were collected and analyzed. To analyze stool flora, 16S ribosomal RNA sequencing was performed. The incidence of chemotherapy-induced diarrhea was lower in the CB group compared with the placebo group. The lymphocyte count and platelet/lymphocyte ratio (PLR) was markedly altered between the two groups. Neutrophil/lymphocyte ratio (NLR) and PLR decreased within the CB group. At week 3, the lymphocyte/monocyte ratio (LMR) was higher in the CB group compared with the placebo group. Alterations in lymphocyte subsets and immunoglobulin levels were not significantly different. Albumin (ALB) level and weight did not differ significantly between the two groups. At 3 weeks the total flora diversity did not decrease in either group. Phyla in the CB group varied slightly, while the proportion of Firmicutes in the placebo group decreased significantly. No statistically significant difference was observed between the two groups, though the genera producing short-chain fatty acids tended to increase, and the pathogenic genera tended to decrease in the CB group, which was almost the opposite of the observation in the placebo group. Operational taxonomy unit analysis revealed a notable increase in beneficial flora, including the Clostridium and Lactobacillus genera of the CB group, compared with the placebo group. The present study highlighted that C. butyricum reduced chemotherapy-induced diarrhea in patients with lung cancer, reduced the systemic inflammatory response system and encouraged homeostatic maintenance.