[Regulatory effects of peroxisome proliferator-activated receptor gamma on the growth of pancreatic carcinoma].

Abstract

OBJECTIVE:

To examine the effects of peroxisome proliferator-activated receptor (PPAR)gamma activation on the growth of human pancreatic carcinoma both in vitro and in vivo.

METHODS:

The expression of PPARgamma and RXRalpha were examined by RT-PCR. SW1990 pancreatic cancer cells were treated with 9-cis-RA, ligand of PPARgamma, 15d-PGJ(2), and both. Antiproliferative effect was evaluated with cell viability by using MTT assay. Pancreatic cancer xenograft tumor model was established in nude mice by inoculating SW1990 cells subcutaneously and rosiglitazone, a PPARgamma activator, was administered via water drinking in experimental group. The nude mice were sacrificed after 75 days, the volume and weight of the xenograft tumor were measured. Expression of PCNA was observed by immunohistochemical staining.

RESULTS:

RT-PCR showed that PPARgamma and RXRalpha mRNA were expressed in SW1990 cell line. MTT assay demonstrated that 15d-PGJ(2), 9-cis-RA and the combination of both had a potent inhibitory effect on the growth of SW1990 cells with a dose-dependent manner. SW1990 cells were suppressed to more than 50% of the control at the concentration of 10 micro mol/L 15d-PGJ(2), 20 micro mol/L 9-cis-RA and 5 micro mol/L 15d-PGJ(2) plus 10 micro mol/L 9-cis-RA, respectively. 9-cis-RA had a synergic action with 15d- PGJ(2) on the growth inhibition of pancreatic carcinoma. In vivo studies, rosiglitazone suppressed the growth of pancreatic carcinoma in a statistically significant manner (P < 0.05). The average tumor volume and tumor weight in the experimental group were less than those in the control group, the growth inhibition rate of rosiglitazone was 80.7%. PCNA was present in both groups, but immunohistochemistry showed a down-regulation trend of PCNA in the experimental group as compared with the control group.

CONCLUSIONS:

Activation of PPARgamma exerts a negative regulatory effect on the growth of pancreatic carcinoma both in vitro and in vivo. These results suggest that PPARgamma might be a novel therapeutic target for the pancreatic carcinoma. Activation of RXRalpha has a synergic action with PPARgamma agonist on the growth inhibition of pancreatic carcinoma.

• Authors: Yu-wei Dong, Xing-peng Wang, Kai Wu, Li-ying Wu, Ru-ling Zhang
• Journal: Zhonghua nei ke za zhi (Zhonghua Nei Ke Za Zhi) Vol. 42 Issue 7 Pg. 479-82 (Jul 2003) ISSN: 0578-1426 [Print] China
• PMID: 12921608 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• PPAR gamma
• Proliferating Cell Nuclear Antigen
• RNA, Messenger
• Retinoid X Receptor alpha

Topics

• Animals
• Cell Division (drug effects)
• Female
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• PPAR gamma (biosynthesis, genetics)
• Pancreatic Neoplasms (metabolism, pathology)
• Proliferating Cell Nuclear Antigen (biosynthesis, genetics)
• RNA, Messenger (genetics)
• Retinoid X Receptor alpha (biosynthesis, genetics)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays