Tiam1 siRNA enhanced the sensitivity of sorafenib on esophageal squamous cell carcinoma in vivo.
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.
Integrated TCM and Western Medicine Department, the Affiliated Tumor Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou, 450008, Henan, People's Republic of China.
Huaimin
H
Liu
Xin
X
Wang
Guirong
G
Shi
Lifeng
L
Jiang
Xiaoli
X
Liu
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis; D004938:Esophageal Neoplasms / Q000473:pathology / Q000628:therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D020662:Guanine Nucleotide Exchange Factors / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000235:genetics*; D000077157:Sorafenib; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C436291:CDKN1B protein, human; D020662:Guanine Nucleotide Exchange Factors; D019394:Ki-67 Antigen; D010671:Phenylurea Compounds; D034741:RNA, Small Interfering; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D009536:Niacinamide; D000077157:Sorafenib