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- Title
miR-143 Overexpression Impairs Growth of Human Colon Carcinoma Xenografts in Mice with Induction of Apoptosis and Inhibition of Proliferation.
- Authors
Borralho, Pedro M.; Simõ es, André E. S.; Gomes, Sofia E.; Lima, Raquel T.; Carvalho, Tâ nia; Ferreira, Duarte M. S.; Vasconcelos, Maria H.; Castro, Rui E.; Rodrigues, Cecília M. P.
- Abstract
Background: MicroRNAs (miRNAs) are aberrantly expressed in human cancer and involved in the (dys)regulation of cell survival, proliferation, differentiation and death. Specifically, miRNA-143 (miR-143) is down-regulated in human colon cancer. In the present study, we evaluated the role of miR-143 overexpression on the growth of human colon carcinoma cells xenografted in nude mice (immunodeficient mouse strain: N: NIH(s) II-nu/nu). Methodology/Principal Findings: HCT116 cells with stable miR-143 overexpression (Over-143) and control (Empty) cells were subcutaneously injected into the flanks of nude mice, and tumor growth was evaluated over time. Tumors arose ∼ 14 days after tumor cell implantation, and the experiment was ended at 40 days after implantation. miR-143 was confirmed to be significantly overexpressed in Over-143 versus Empty xenografts, by TaqManH&rag; Real-time PCR (p,0.05). Importantly, Over- 143 xenografts displayed slower tumor growth compared to Empty xenografts from 23 until 40 days in vivo (p,0.05), with final volumes of 928±338 and 2512±387 mm3, respectively. Evaluation of apoptotic proteins showed that Over-143 versus Empty xenografts displayed reduced Bcl-2 levels, and increased caspase-3 activation and PARP cleavage (p,0.05). In addition, the incidence of apoptotic tumor cells, assessed by TUNEL, was increased in Over-143 versus Empty xenografts (p,0.01). Finally, Over-143 versus Empty xenografts displayed significantly reduced NF-kB activation and ERK5 levels and activation (p,0.05), as well as reduced proliferative index, evaluated by Ki-67 immunohistochemistry (p,0.01). Conclusions: Our results suggest that reduced tumor volume in Over-143 versus Empty xenografts may result from increased apoptosis and decreased proliferation induced by miR-143. This reinforces the relevance of miR-143 in colon cancer, indicating an important role in the control of in vivo tumor progression, and suggesting that miR-143 may constitute a putative novel therapeutic tool for colon cancer treatment that warrants further investigation
- Subjects
CANCER; XENOGRAFTS; LABORATORY mice; APOPTOSIS; CELL proliferation; COLON cancer; CANCER invasiveness; IMMUNOHISTOCHEMISTRY
- Publication
PLoS ONE, 2011, Vol 6, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0023787