Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice

• Published in: Chinese medical journal 2011-09, Vol.124 (17), p.2708-2714
• Main Authors: Lu, Tai-ying, Li, Wen-cai, Chen, Ren-yin, Fan, Qing-xia, Wang, Liu-xing, Wang, Rui-lin, Lu, Shi-xin, Meng, Hui
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Cell Line, Tumor; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - metabolism; Humans; Immunohistochemistry; Mice; Mice, Nude; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Real-Time Polymerase Chain Reaction; Tretinoin - therapeutic use; Vascular Endothelial Growth Factor A - metabolism; Xenograft Model Antitumor Assays; 体内; 全反式维甲酸; 抑制作用; 血管内皮生长因子; 血管生成抑制; 裸鼠; 食管; 鳞状细胞癌
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.2011.17.026

Background The potential application of retinoic acid receptor activators, such as all trans-retinoic acid （ATRA）, for treating various cancers have been studied both pre-clinically and clinically. Whether ATRA has an anticancer effect on human esophageal squamous cancer cell （ESCC） is still unknown. We have explored the anticancer effect of ATRA in ESCC, and in this study, the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor （VEGF） signal transduction pathway in transplantable tumor growth of the human ESCC cell line, EC9706, in nude mice. Methods The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice. Reverse transcription-polymerase chain reaction （RT-PCR）, Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues. Results Compared to the control group, the tumor inhibition rates in the low dose ATRA, high dose ATRA, and 5-FU groups were 83.21%, 88.32%, 91.02%, respectively. The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group （P 〈0.05）. The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31, CD34, and CD105 （component of the TGF-13 receptor） in ESCC xenograft tissues （P 〈0.05）. Conclusions ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice. These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction, which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.