A novel steroid and xenobiotic receptor (SXR) may be involved in chemoresistance, and we studied this receptor in endometrial cancer cell lines. The cisplatin (CDDP)-sensitive Ishikawa cell line and its CDDP-resistant sub-clone (ISIW+) were used. ISIW+ cells showed a much higher SXR expression. When Ishikawa cells were cultured with SXR anti-sense oligonucleotides (AS), the cells failed to pass crisis and did not gain cisplatin resistance. In an experiment using SCID mice, all AS-treated animals survived, whereas controls had 50% survival at 35 days. The present data indicate that SXR is a key system to induce, maintain and reverse a cisplatin-resistant phenotype in endometrial cancer cells.
VermorkenJBHoekmanK: Chemotherapy for gynecologic malignancies. Curr Opin Oncol1995; 7: 457–465.
2.
OzolsRFVermorkenJB: Chemotherapy of advanced ovarian cancer: current status and future directions. Semin Oncol1997; 24 (Suppl 2): 1–9.
3.
PiergaJYDierasVParaisoDPouillartP: Chemotherapy of metastatic endometrial carcinoma. Review of the literature. Bull Cancer1995; 82: 1005–1018.
4.
HarriesMGoreM: Part I: Chemotherapy for epithelial ovarian cancer-treatment at first diagnosis. Lancet Oncol2002; 3: 529–536.
5.
HarriesMGoreM: Part II: Chemotherapy for epithelial ovarian cancer-treatment of recurrent disease. Lancet Oncol2002; 3: 537–545.
6.
NakayamaYSakamotoHYamamotoT: Establishment and characterization of CDDP resistant sub-clone from Ishikawa endometrial cells. Hum Cells2003 (in press).
7.
FalknerKCPinaireJAXiaoGHGeogheganTEProughRA: Regulation of the rat glutathione S-transferase A2 gene by glucocorticoids: involvement of both the glucocorticoid and pregnane X receptors. Mol Pharmacol2001; 60: 611–619.
8.
NisidaMKasaharaKKanekoMIwasakiHHayashiK: Establishment of a new human endometrial adenocarcinoma cell line, Ishikawa cells, containing estrogen and progesterone receptors (in Japanese). Nippon Sanka Fujinka Gakkai Zasshi1985; 37: 1103–1111.
9.
KatoTSakaiMMuramatsuM: Structure and expression of a human class pi glutathione S-transferase messenger RNA. Cancer Res1987; 47: 5626–5630.
10.
KliewerSAMooreJTWadeLStaudingerJLWatsonMAJonesSA: An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell1998; 92: 73–82.
11.
LehmannJMMcKeeDDWatsonMAWillsonTMMooreJTKliewerSA: The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest1998; 102: 1016–1023.
12.
MurrayM: Mechanisms and significance of inhibitory drug interactions involving cytochrome P450 enzymes. Int J Mol Med1999; 3: 227–238.
13.
KastHRGoodwinBTarrPTJonesSAAnisfeldAMStoltzCM: Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem2002; 277: 2908–2915.
14.
GotoSIidaTChoSOkaMKohnoSKondoT.Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells. Free Radic Res1999; 31: 549–558.
15.
GotoSIharaYUrataYIzumiSAbeKKojiT: Doxorubicin-induced DNA intercalation and scavenging by nuclear glutathione S-transferase pi. FASEB J2001; J15: 2702–2714.
16.
MayrDPannekampUBarettonGBGroppMMeierWFlensMJ: Immunohistochemical analysis of drug resistance-associated proteins in ovarian carcinomas. Pathol Res Pract2000; 196: 469–475.
17.
BarnetteKGSarkarMAGloverDDLiPBoydCLalkaD: Glutathione S-transferase in human endometrium: quantitation and interindividual variability in isoform content. Gynecol Obstet Invest1999; 47: 114–119.
18.
JeronimoCVarzimGHenriqueROliveiraJBentoMJSilvaC: I105V polymorphism and promoter methylation of the GSTP1 gene in prostate adenocarcinoma. Cancer Epidemiol Biomarkers Prev2002; 11: 445–450.
