Intravenous KITENIN shRNA Injection Suppresses Hepatic Metastasis and Recurrence of Colon Cancer in an Orthotopic Mouse Model.
10.3346/jkms.2011.26.11.1439
- Author:
Jun Eul HWANG
1
;
Hyun Jeong SHIM
;
Young Kyu PARK
;
Sang Hee CHO
;
Woo Kyun BAE
;
Dae Eun KIM
;
Kyung Keun KIM
;
Ik Joo CHUNG
Author Information
1. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea. ijchung@jnu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
KITENIN;
Colon cancer;
Short hairpin RNA;
Firefly luciferase;
Metastasis
- MeSH:
Animals;
Carrier Proteins/*genetics/metabolism;
Cell Line, Tumor;
Colonic Neoplasms/genetics/mortality/pathology/*therapy;
Disease Progression;
Liver Neoplasms/prevention & control/*secondary;
Membrane Proteins/*genetics/metabolism;
Mice;
Mice, Inbred BALB C;
Neoplasm Metastasis/*prevention & control;
Neoplasm Recurrence, Local/genetics/*prevention & control;
RNA Interference;
RNA, Small Interfering/*therapeutic use;
Tumor Markers, Biological/genetics
- From:Journal of Korean Medical Science
2011;26(11):1439-1445
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
