The Expression Of PPARs In Endometrial Cancer And The Effect Of Its' Ligand On Inhibition Of Endometrial Cancer Cell Cultured In Vitro

Objective: Endometrial cancer is the most common gynecologic malignancy, frequently arising in association with obesity and diabetes mellitus. In this study, we evaluated the correlation between endometrial carcinoma and peroxisome proliferator-activated receptors (PPARs) expression and assessed whether PPARγ ligands influence carcinoma growth.Methods:1.PPARs mRNA expression was detected by reverse transcriptase polymerase chain reaction in endometrial carcinoma cell lines.2.Then we examined the presence and cellular distribution of PPARs protein in 20 normal endometria, 10 endometria with hyperplasia, and 30 endometria with endometrial carcinoma by immunohistochemistry.3.We subsequently confirmed expression of PPARs protein by immunoblotting in 20 normal endometria, 10 endometria with hyperplasia, and 30 endometria with endometrial carcinoma.4.We further examined the effects of PPARγ agonist Rosiglitazone to endometrial carcinoma cell lines. Cell proliferation was measured by MTT colorimetric assay.5.Cell cycle percentage were detected by flow cytometry.6.Apoptotic cells were detected by the methods of TUNEL assay.Results: 1. PPARα and PPARγ mRNA expression was detected in HHUA and KLE cellline,but without PPARβ mRNA expression.2.Specific immunostaining for PPARα and PPARγ protein was seen in most ofendometrial cancer, but in none of the benign endometrial sections (P < 0.01).Immunostaining for PPARα protein was localized to the epithelial tumor cells andwas cytoplasmic rather than nuclear. The expression of PPARα and PPARγ proteinsincreased gradually as the endometrium progresses from simple hyperplasia toatypical hyperplasia and endometrioid adenocarcinoma. PPARα and PPARγ wereoverexpressed in endometrial cancer tissues and the expression enhanced asdifferentiation worsened. The expression of PPARα and PPARγ in endometrioidadenocarcinoma was positively correlated to clinical-pathological stage, grade,myometrial infiltration and metastasis and demonstrated that the two proteins wererelated to the prognosis of endometrioid adenocarcinoma and their expression may bea prognostic factor of endometrial cancer.3. The result of Western blot indicate that the expression of PPARα and PPARγproteins increased gradually as the endometrium progresses from simple hyperplasiato atypical hyperplasia and endometrioid adenocarcinoma. PPARα and PPARγ wereoverexpressed in endometrial cancer tissues and the expression enhanced as cancergrade increased.4.Rosiglitazone significantly inhibited endometrial cell growth in adose-dependent manner and a time-dependent manner.5.After treatment with Rosiglitazone, the cell cycle arrested at G₁ phase anddecreased the S phase fraction.6.Endometrial cancer cells showed typical apoptosis changes after PPARγactivation. The apoptosis rate was(18.3±1.9)% after treatment with 200umol/Lrosiglitazone for 24h.The difference was significant compared withcontrol[(2.66±0.49)%,P<0.05]Conclusions:1.The expression of PPARα and PPARγ proteins increased gradually as theendometrium progresses from simple hyperplasia to atypical hyperplasia and endometrioid adenocarcinoma. PPARα and PPARγ were overexpressed in endometrial cancer tissues and the expression enhanced as cancer grade increased .The expression of PPARα and PPARγ in endometrioid adenocarcinoma was positively correlated to clinical-pathological stage, grade, myometrial infiltration and metastasis and demonstrated that the two proteins were related to the prognosis of endometrioid adenocarcinoma and their expression may be a prognostic factor of endometrial cancer.2.In the present study it is suggested that Rosiglitazone inhibit the proliferation of endometrial carcinoma cell in vitro , its anti-cancer effect seems to be due to induction of apoptosis which may be a result of up-regulating PPARγ.