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KMID : 0191120110260111439
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Journal of Korean Medical Science
2011 Volume.26 No. 11 p.1439 ~ p.1445
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Intravenous KITENIN shRNA Injection Suppresses Hepatic Metastasis and Recurrence of Colon Cancer in an Orthotopic Mouse Model
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Hwang Jun-Eul
Shim Hyun-Jeong
Park Young-Kyu
Cho Sang-Hee
Bae Woo-Kyun
Kim Dae-Eun
Kim Kyung-Keun
Chung Ik-Joo
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Abstract
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KITENIN (KAI1 C-terminal interacting tetraspanin) promotes invasion and metastasis in mouse colon cancer models. In the present study, we evaluated the effects of KITENIN knockdown by intravenous administration of short hairpin RNAs (shRNAs) in an orthotopic mouse colon cancer model, simulating a primary or adjuvant treatment setting. We established orthotopic models for colon cancer using BALB/c mice and firefly luciferase-expressing CT-26 (CT26/Fluc) cells. Tumor progression and response to therapy were monitored by bioluminescence imaging (BLI). In the primary therapy model, treatment with KITENIN shRNA substantially delayed tumor growth (P = 0.028) and reduced the incidence of hepatic metastasis (P = 0.046). In the adjuvant therapy model, KITENIN shRNA significantly reduced the extent of tumor recurrence (P = 0.044). Mice treated with KITENIN shRNA showed a better survival tendency than the control mice (P = 0.074). Our results suggest that shRNA targeting KITENIN has the potential to be an effective tool for the treatment of colon cancer in both adjuvant and metastatic setting.
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KEYWORD
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KITENIN, Colon cancer, Short hairpin RNA, Firefly luciferase, Metastasis
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