Toll-like receptor 4 signaling activated by lipopolysaccharide-induced autophagy in esophageal squamous cell carcinoma promotes tumor proliferation and S phase arrested
10.13699/j.cnki.1001-6821.2017.24.015
- VernacularTitle:脂多糖激活Toll样受体4介导自噬促进食管鳞癌细胞增殖与细胞周期S期阻滞的研究
- Author:
Juan LIU
1
;
Wei SUN
;
Yu-Kun ZU
Author Information
1. 武汉大学人民医院老年病科,武汉430060
- Keywords:
lipopolysaccharide;
Toll like receptor 4;
esophageal squamous cell carcinoma
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(24):2610-2614
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expressions of Toll like receptor 4 (TLR4) in esophageal squamous cell carcinoma (ESCC) and para-carcinoma tissues,and to elucidate the regulation of lipopolysaccharides (LPS) to TLR4 expression in ESCC cell lines,and the influence to autophagy,proliferation and cell cycling.Methods The expression characters and proportions of TLR4 were detected by immunohistochemical analysis in 50 ESCC and 50 para-carcinoma samples.Test group was treated with 1 μg · mL-1 LPS and control group was treated with cell culture medium only.Si-NC group was treated with siRNA-negative control and si-TLR4 group was treated with siRNA-TLR4.The regulation of LPS to TLR4 and autophagy related molecules like LC-3,ATG5 and ATG7 were detected in Eca-109 and TE-1 cell lines.Furthermore,the effects on proliferation and cell cycling after TLR4-knockdown were analyzed by CCK8 and flow cytometry.Results Overexpression of TLR4 was detected by immunohistochemical analysis in 68,00％ of the ESCC samples,compared to 36.00％ in para-carcinoma tissues (P ＜0.01).Relative protein expression of TLR4 in control group and test group in Eca-109 cells and TE-1 cells were (0.11 ±0.05),(0.35 ±0.12) and (0.07 ±0.02),(0.41 ±0.10),the differences were statistically significant (all P ＜ 0.0.5) Activation of TLR4 by LPS up-regulated autophagy related molecules LC-3,ATG5 and ATG7.TLR4-knockdown inhibited proliferation and blocked the cell cycle during S phase in ESCC cell lines.Survival rates of in day 5 of Eca-109 and TE-1 cell lines in siRNA-negative control and si-TLR4 groups were (1.35 ± 0.02),(0.92 ± 0.04) and (1.35 ± 0.02),(0.87 ± 0.04) with significant difference (all P ＜ 0.0.5).Conclusion Higher expression of TLR4 in carcinoma tissues reveals important functions of TLR4 signaling in ESCC development.TLR4 signaling activated by LPS induced autophagy in ESCC cell lines promotes tumor proliferation and S phase arrested.In autophagy prospective,TLR4 targeting may be a new therapy strategy in ESCC.
