Table 2 Pro-proliferative and anti-apoptotic functions of PXR

Ovarian carcinoma

PXR activation by cognate ligands induced cell proliferation and drug resistance. In SKOV-3 xenografts, PXR ligand activation induced cell proliferation and tumor growth.

[33]

Colon carcinoma

Activation of PXR enhanced cell growth, invasion, and metastasis in human colon tumor cell lines and human colon cancer xenograft models via PXR-mediated FGF19 signaling.

[48]

Breast carcinoma

Immunohistochemistry, quantitative reverse transcriptase PCR, and microarray analysis all revealed PXR expression in carcinoma tissues but not in nonneoplastic or stromal cells in breast carcinoma patient samples. In breast carcinoma cells, pharmacologic activation of PXR via rifampicin increased PXR target genes (OATP1A2 and CYP3A4). Positive correlation between PXR, OATP1A2, and increasing tumor grade in breast carcinoma patient samples.

[26]

Anti-apoptotic functions of PXR

Tissue specification

PXR activation approach

References

Colon cancer

PXR activation via a genetic approach (constitutive activation) or pharmacologic activation via rifampicin protected colon cancer cells from chemically induced apoptosis. PXR activation in transgenic mice inhibited bile acid-induced colonic epithelial apoptosis and sensitized mice to dimethylhydrazine-induced colon carcinogenesis.

[35]

Hepatocytes/Hepatoma cells

Agonists of PXR increased hepatocyte viability and protected them from staurosporine-induced apoptosis via the induction of Bcl-2 and Bcl-xl in human and rat hepatocytes. PXR agonists protected HepG2 human hepatoma cells from Fas-induced apoptosis via Bcl-2 and Bcl-xl induction.

[34]

Prostate cancer

PXR activation via a potent selective PXR agonist, SR12813, increased resistance to chemotherapeutics paclitaxel and vinblastine. Knockdown of PXR via shRNA decreased resistance and increased sensitivities to chemotherapeutics.

[32]

Endometrial cancer

PXR overexpression caused significant decreases in apoptosis in the presence of paclitaxel or cisplatin. PXR downregulation enhanced apoptosis in the presence of paclitaxel, cisplatin, and medroxyprogesterone acetate.

[36]