Gene silencing of beta-catenin by RNAi inhibits cell proliferation in human esophageal cancer cells in vitro and in nude mice.
beta-Catenin, which is frequently overexpressed in a variety of human cancers including esophageal cancer, mediates cancer cell proliferation and tumor growth. In the present study, we used a human U6 promoter-driven DNA-template approach to induce short hairpin RNA (shRNA)-triggered RNA interference to silence beta-catenin gene expression in human esophageal squamous cell carcinoma cell line Eca-109, and then evaluated its effects on the proliferation and growth of tumor cells in vitro and in nude mice. beta-Catenin expression levels decreased markedly in Eca-109 cells transfected with a plasmid expressing shRNA for beta-catenin. Downregulation of beta-catenin was concomitantly accompanied by reduction of cyclin D1, colony formation, and growth inhibition of Eca-109 cells in vitro. The mechanism appears to be the G0/G1 phase arrest but not induction of apoptosis. In vivo, treatment of Eca-109 cells with beta-catenin shRNA greatly impeded tumor growth in nude mice. We conclude that plasmid vector-mediated beta-catenin RNA interference holds great promise as a novel treatment on human esophageal cancer with beta-catenin overexpression.
Wang
Jin-Sheng
JS
Department of Pathology, Xiangya Medical College, Central South University, Changsha, China.
Zheng
Chang-Li
CL
Wang
Yong-Jin
YJ
Wen
Ji-Fang
JF
Ren
Hong-Zheng
HZ
Liu
Ying
Y
Jiang
Hai-Ying
HY
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000502:physiology; D016193:G1 Phase / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics*; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
D034741:RNA, Small Interfering; D051176:beta Catenin; D019938:Cyclin D1; D053148:Caspase 3