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Knockdown of PPAR δ Gene Promotes the Growth of Colon Cancer and Reduces the Sensitivity to Bevacizumab in Nude Mice Model
West China Hospital, Sichuan University, China.
West China Hospital, Sichuan University, China.
West China Hospital, Sichuan University, China.
West China Hospital, Sichuan University, China.
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2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 4Article in journal (Refereed) Published
Abstract [en]

The role of peroxisome proliferator – activated receptor- δ (PPAR δ) gene in colon carcinogenesis remains highly controversial. Here, we established nude mice xenograft model using a human colon cancer cell line KM12C either with PPAR δ silenced or normal. The xenografts in PPAR δ-silenced group grew significantly larger and heavier with less differentiation, promoted cell proliferation, increased expression of vascular endothelial growth factor (VEGF) and similar apoptosis index compared with those of PPAR δ-normal group. After treated with the specific VEGF inhibitor bevacizumab, the capacities of growth and proliferation of xenografts were decreased in both groups while still significantly higher in PPAR δ-silenced group than in PPAR δ-normal group. Administration of PPAR δ agonist significantly decreased VEGF expression in PPAR δ-normal KM12C cells but not in PPAR δ-silenced cells. These findings demonstrate that, knockdown of PPAR δ promotes the growth of colon cancer by inducing less differentiation, accelerating the proliferation and VEGF expression of tumor cells in vivo, and reduces tumor sensitivity to bevacizumab. This study indicates that PPAR δ attenuates colon carcinogenesis.

Place, publisher, year, edition, pages
Public Library of Science , 2013. Vol. 8, no 4
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-93397DOI: 10.1371/journal.pone.0060715ISI: 000317898000054OAI: diva2:624482

Funding Agencies|Natural Science Foundation of China|30801332|Ph.D. Programs Foundation of Ministry of Education of China|200806100058|Swedish Cancer Foundation||

Available from: 2013-05-31 Created: 2013-05-31 Last updated: 2014-08-26

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Sun, Xiaofeng
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OncologyFaculty of Health SciencesDepartment of Oncology
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