title: Knockdown of PPAR δ gene promotes the growth of colon cancer and reduces the sensitivity to bevacizumab in nude mice model.
abstract: 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.
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Yang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.forename: Qin
authors.initials: Q
authors.lastname: Ma
authors.forename: Cun
authors.initials: C
authors.lastname: Wang
authors.forename: Keling
authors.initials: K
authors.lastname: Chen
authors.forename: Wenjian
authors.initials: W
authors.lastname: Meng
authors.forename: Yongyang
authors.initials: Y
authors.lastname: Yu
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D047495:PPAR gamma / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D047495:PPAR gamma; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab