Effects of upregulation of CREB on proliferation, invasion and NK cell killing activity of esophageal adenocarcinoma / 中国医师杂志

ABSTRACT

Objective:To investigate the effects of upregulation of cAMP response element binding protein (CREB) on proliferation, invasion and natural killer (NK) cell killing activity of esophageal adenocarcinoma.Methods:23 patients with esophageal cancer treated in Shaanxi Provincial People′s Hospital from March 2017 to December 2019 were selected. The protein expression of CREB in esophageal adenocarcinoma and adjacent normal tissues was detected by immunohistochemistry; Esophageal adenocarcinoma cell line TE-10 was cultured in vitro. TE-10 cells transfected with si-NC were set as the control group and TE-10 cells transfected with si-CREB were set as the si-CREB group. Western blot was used to detect the protein level of CREB, MHC class Ⅰ chain-related A (MICA) and MHC class Ⅰ chain-related B (MICB); Flow cytometry was employed to detect the expression of MICA and MICB; clone formation experiment and Transwell were used to detect the proliferative and invasive ability of TE-10 cells; lactate dehydrogenase (LDH) releasing assay was used to detect cytotoxicity of NK cells against TE-10 cells. Results:The expression of CREB in esophageal adenocarcinoma tissue was higher than that in normal tissues adjacent to cancer; the protein level of CREB in esophageal cancer cell TE-10 was higher than that of human normal esophageal epithelial cells HEEC ( P<0.05). The proliferative and invasive ability of TE-10 cells in the si-CREB group was significant lower than that in the control group ( P<0.05), while the expression of MICA and MICB, the killing rate of NK cells on TE-10 cells was significant higher than that in the control group ( P<0.05). Conclusions:CREB was highly expressed in esophageal adenocarcinoma tissues and cells. Silencing CREB could inhibit the proliferation and invasion of esophageal adenocarcinoma cells, and enhance the killing sensitivity of NK cells to esophageal adenocarcinoma cells by up-regulating the expression of MICA and MICB.