title: Activation of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits hepatoma cell growth via downregulation of SEPT2 expression.
abstract: Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis and low therapeutic efficacy. Recent studies have demonstrated the therapeutic prospect of peroxisome proliferator-activated receptor-γ (PPARγ) cancer angiogenesis. However, the action mechanisms remain elusive. In the present study, by using mass spectrometry, we found that PPARγ ligand rosiglitazone (RGZ) could regulate HCC cell growth by influencing various downstream factors and pathways. Among the altered proteins, septin 2 (SEPT2) was found to exhibit oncogenic function. PPARγ overexpression could inhibit the expression of SEPT2, thus blocking the promoting effects of SEPT2 on HCC cell proliferation, invasion and its inhibitory effect on cell apoptosis. Further studies also indicated that SEPT2 promoted HCC cell growth via upregulation of matrix metalloproteinase (MMP)-2 and -9, and simultaneously inhibited the cleavage of caspase-3, -7, and -9. Interestingly, the effects of SEPT2 on the above factors could be suppressed by PPARγ overexpression, suggesting that PPARγ could inhibit HCC cell growth via regulating the expression and blocking the oncogenic function of SEPT2. Taken together, these results provide new evidence for the action mechanisms of PPARγ in carcinogenesis of HCC, and upon further investigation, PPARγ could be developed as a new target for the treatment of liver cancer.
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China. Electronic address: clq0829@163.com.
authors.forename: Liang-Qi
authors.initials: LQ
authors.lastname: Cao
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China.
authors.forename: Zi-Li
authors.initials: ZL
authors.lastname: Shao
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China.
authors.forename: Hui-Hong
authors.initials: HH
authors.lastname: Liang
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China.
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xue
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019295:Computational Biology; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D000077154:Rosiglitazone; D058112:Septins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D045162:Thiazolidinediones / Q000494:pharmacology*; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C505407:CASP3 protein, human; C505520:CASP7 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C000602252:SEPTIN2 protein, human; D058112:Septins
keywords: Hepatocellular carcinoma; PPARγ; Proteomics; Rosiglitazone; SEPT2; Spectrometry