Tiam1 siRNA enhanced the sensitivity of sorafenib on esophageal squamous cell carcinoma in vivo

• Published in: Tumor biology Vol. 35; no. 8; pp. 8249 - 8258
• Main Authors: Liu, Huaimin, Wang, Xin, Shi, Guirong, Jiang, Lifeng, Liu, Xiaoli
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.08.2014; Springer Nature B.V
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Cell growth; Cell Line, Tumor; Chemotherapy; Cyclin-Dependent Kinase Inhibitor p27 - analysis; Esophageal cancer; Esophageal Neoplasms - pathology; Esophageal Neoplasms - therapy; Esophageal Squamous Cell Carcinoma; Guanine Nucleotide Exchange Factors - analysis; Guanine Nucleotide Exchange Factors - antagonists & inhibitors; Guanine Nucleotide Exchange Factors - genetics; Humans; Ki-67 Antigen - analysis; Male; Mice; Mice, Inbred BALB C; Niacinamide - analogs & derivatives; Niacinamide - therapeutic use; Phenylurea Compounds - therapeutic use; Protein expression; Research Article; Ribonucleic acid; RNA; RNA, Small Interfering - genetics; Sorafenib; T-Lymphoma Invasion and Metastasis-inducing Protein 1; Xenograft Model Antitumor Assays; Tiam1; Cell proliferation; Esophageal squamous cell carcinoma; Nude mice; Sorafenib; Apoptosis
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-2083-x

Our previous study demonstrated that Tiam1 was highly expressed in esophageal squamous cell carcinoma (ESCC) tissues. In the present study, we investigated the therapeutic role of Tiam1 siRNA in combination with sorafenib in xenografted human ESCC. Our results demonstrated that expression of Tiam1 protein in EC9706 cells was significantly higher than those in ESCC cells (Eca109 and EC1) and normal esophageal epithelial cells Het-1A ( P  < 0.05). Tiam1 siRNA markedly suppressed Tiam1 protein expression in tumor tissues of nude mice, but sorafenib did not alter Tiam1 level. In addition, Tiam1 siRNA or sorafenib alone evidently inhibited tumor growth, reduced Ki-67 proliferation index, and induced cell apoptosis in xenografted nude mice, and their combinations had the strongest effect. Notably, Tiam1 siRNA or sorafenib alone obviously increased p27 level, but reduced Mcl-1 and bcl-2 levels in xenografted nude mice, and their combinations reached the best effect. These findings suggest that combination of Tiam1 siRNA with sorafenib may be the novel molecular therapy target for the patients with ESCC.