Progress in the study of the pregnane X receptor in drug resistance in breast cancer

doi:10.3760/cma.j.cn371439-20240422-00098

Abstract

Abstract:

The pregnane X receptor （PXR） is a crucial regulator of cytochrome P-450 （CYP450） expression. It is involved in oxidative stress， steroid and bile acid metabolism， inflammatory response， apoptosis， cell proliferation and other biological behaviors， and also participates in the metabolism， transport and clearance of chemotherapy drugs. After activation， PXR can affect chemotherapy drug resistance of breast cancer through genetic variation and epigenetic modification， regulation of apoptosis， and participation in phosphorylation/dephosphorylation. It may be a potential therapeutic target for patients with breast cancer resistance.

Key words: Breast neoplasms, Pregnane X receptor, Drug resistance

Han Xiaoxu, Zhang Nan, Liu Shuai. Progress in the study of the pregnane X receptor in drug resistance in breast cancer[J]. Journal of International Oncology, 2024, 51(9): 590-594.

References 38

[1]	Kashyap D, Pal D, Sharma R, et al. Global increase in breast cancer incidence: risk factors and preventive measures[J]. Biomed Res Int, 2022, 2022: 9605439. DOI: 10.1155/2022/9605439.
[2]	何思怡, 李贺, 曹毛毛, 等. 全球及我国女性乳腺癌疾病负担年龄分布及变化趋势[J]. 中国肿瘤, 2023, 32(1): 1-7. DOI: 10.11735/j.issn.1004-0242.2023.01.A001.
[3]	Niu X, Wu T, Li G, et al. Insights into the critical role of the PXR in preventing carcinogenesis and chemotherapeutic drug resistance[J]. Int J Biol Sci, 2022, 18(2): 742-759. DOI: 10.7150/ijbs.68724. pmid: 35002522
[4]	Skandalaki A, Sarantis P, Theocharis S. Pregnane X receptor (PXR) polymorphisms and cancer treatment[J]. Biomolecules, 2021, 11(8): 1142. DOI: 10.3390/biom11081142.
[5]	Rao ZZ, Tang ZW, Wen J. Advances in drug resistance of triple negative breast cancer caused by pregnane X receptor[J]. World J Clin Oncol, 2023, 14(9): 335-342. DOI: 10.5306/wjco.v14.i9.335.
[6]	Dai Y, Luo J, Xiang E, et al. Prenatal exposure to retrorsine induces developmental toxicity and hepatotoxicity of fetal rats in a sex-dependent manner: the role of pregnane X receptor activation[J]. J Agric Food Chem, 2021, 69(10): 3219-3231. DOI: 10.1021/acs.jafc.0c06748.
[7]	Wang HB, Chu F, Zhang XF, et al. TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs[J]. Cell Death Dis, 2023, 14(1): 64. DOI: 10.1038/s41419-022-05537-7.
[8]	Kamaraj R, Drastik M, Maixnerova J, et al. Allosteric antagonism of the pregnane X receptor (PXR): current-state-of-the-art and prediction of novel allosteric sites[J]. Cells, 2022, 11(19): 2974. DOI: 10.3390/cells11192974.
[9]	Matheux A, Gassiot M, Fromont G, et al. PXR modulates the prostate cancer cell response to afatinib by regulating the expression of the monocarboxylate transporter SLC16A1[J]. Cancers (Basel), 2021, 13(14): 3635. DOI: 10.3390/cancers13143635.
[10]	Rigalli JP, Theile D, Nilles J, et al. Regulation of PXR function by coactivator and corepressor proteins: ligand binding is just the beginning[J]. Cells, 2021, 10(11): 3137. DOI: 10.3390/cells10113137.
[11]	Sári Z, Mikó E, Kovács T, et al. Indolepropionic acid, a metabolite of the microbiome, has cytostatic properties in breast cancer by activating AHR and PXR receptors and inducing oxidative stress[J]. Cancers (Basel), 2020, 12(9): 2411. DOI: 10.3390/cancers12092411.
[12]	Shao Z, Li Y, Dai W, et al. ETS-1 induces Sorafenib-resistance in hepatocellular carcinoma cells via regulating transcription factor activity of PXR[J]. Pharmacol Res, 2018, 135: 188-200. DOI: 10.1016/j.phrs.2018.08.003. pmid: 30114438
[13]	Yang H, Ren L, Wang Y, et al. FBI-1 enhanced the resistance of triple-negative breast cancer cells to chemotherapeutic agents via the miR-30c/PXR axis[J]. Cell Death Dis, 2020, 11(10): 851. DOI: 10.1038/s41419-020-03053-0.
[14]	Sun J, Pang MD, Tang XZ, et al. Anti-tumor effect of gambogenic acid and its effect on CYP2C and CYP3A after oral administration[J]. Chem Pharm Bull (Tokyo), 2023, 71(5): 334-341. DOI: 10.1248/cpb.c22-00656. pmid: 36858593
[15]	Qiao EQ, Yang HJ, Yu XF, et al. Curcuma zedoaria petroleum ether extract reverses the resistance of triple-negative breast cancer to docetaxel via pregnane X receptor[J]. Ann Transl Med, 2021, 9(17): 1389. DOI: 10.21037/atm-21-4199.
[16]	Wen J, Lv Z, Ding H, et al. Association between PXR polymorphisms and cancer risk: a systematic review and meta-analysis[J]. Biosci Rep, 2018, 38(3): BSR20171614. DOI: 10.1042/BSR20171614.
[17]	Revathidevi S, Sudesh R, Vaishnavi V, et al. Screening for the 3'UTR polymorphism of the PXR gene in South Indian breast cancer patients and its potential role in pharmacogenomics[J]. Asian Pac J Cancer Prev, 2016, 17(8): 3971-3977.
[18]	Li Y, Zhou Y, Mao F, et al. miR-452 reverses abnormal glycosy-lation modification of ERα and estrogen resistance in TNBC (triple-negative breast cancer) through targeting UGT1A1[J]. Front Oncol, 2020, 10: 1509. DOI: 10.3389/fonc.2020.01509.
[19]	Theocharis S, Giaginis C, Gourzi S, et al. High pregnane X receptor (PXR) expression is correlated with poor prognosis in invasive breast carcinoma[J]. Diagnostics (Basel), 2021, 11(11): 1946. DOI: 10.3390/diagnostics11111946.
[20]	Li T, Kong A, Ma Z, et al. Protein arginine methyltransferase 1 may be involved in pregnane x receptor-activated overexpression of multidrug resistance 1 gene during acquired multidrug resistant[J]. Oncotarget, 2016, 7(15): 20236-20248. DOI: 10.18632/oncotarget.7752. pmid: 26934120
[21]	Sultana H, Kato A, Ohashi A, et al. Effect of vitamin K-mediated PXR activation on drug-metabolizing gene expression in human intestinal carcinoma LS180 cell line[J]. Nutrients, 2021, 13(5): 1709. DOI: 10.3390/nu13051709.
[22]	Madejczyk AM, Canzian F, Góra-Tybor J, et al. Impact of genetic polymorphisms of drug transporters ABCB1 and ABCG2 and regulators of xenobiotic transport and metabolism PXR and CAR on clinical efficacy of dasatinib in chronic myeloid leukemia[J]. Front Oncol, 2022, 12: 952640. DOI: 10.3389/fonc.2022.952640.
[23]	Gautam S, Singh P, Singh M, et al. Rifaximin, a pregnane X receptor (PXR) activator regulates apoptosis in a murine model of breast cancer[J]. RSC Adv, 2018, 8(7): 3512-3521. DOI: 10.1039/c7ra09689e.
[24]	Oladimeji PO, Wright WC, Wu J, et al. RNA interference screen identifies NAA10 as a regulator of PXR transcription[J]. Biochem Pharmacol, 2019, 160: 92-109. DOI: 10.1016/j.bcp.2018.12.012. pmid: 30566892
[25]	Jiang Y, Feng D, Ma X, et al. Pregnane X receptor regulates liver size and liver cell fate by yes-associated protein activation in mice[J]. Hepatology, 2019, 69(1): 343-358. DOI: 10.1002/hep.30131. pmid: 30048004
[26]	Xing YQ, Yan J, Niu YD. PXR: a center of transcriptional regulation in cancer[J]. Acta Pharm Sin B, 2020, 10(2): 197-206. DOI: 10.1016/j.apsb.2019.06.012. pmid: 32082968
[27]	Yan L, Chen Z, Wu L, et al. Inhibitory effect of PXR on ammonia-induced hepatocyte autophagy via P53[J]. Toxicol Lett, 2018, 295: 153-161. DOI: 10.1016/j.toxlet.2018.06.1066. pmid: 29908302
[28]	Ming WH, Luan ZL, Yao Y, et al. Pregnane X receptor activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/β-catenin signaling[J]. Acta Pharmacol Sin, 2023, 44(10): 2075-2090. DOI: 10.1038/s41401-023-01113-7.
[29]	Rosenthal SB, Bush KT, Nigam SK. A network of SLC and ABC transporter and DME genes involved in remote sensing and signaling in the gut-liver-kidney axis[J]. Sci Rep, 2019, 9(1): 11879. DOI: 10.1038/s41598-019-47798-x.
[30]	Hammer H, Schmidt F, Marx-Stoelting P, et al. Cross-species analysis of hepatic cytochrome P450 and transport protein expression[J]. Arch Toxicol, 2021, 95(1): 117-133. DOI: 10.1007/s00204-020-02939-4. pmid: 33150952
[31]	Fritz A, Busch D, Lapczuk J, et al. Expression of clinically relevant drug-metabolizing enzymes along the human intestine and their correlation to drug transporters and nuclear receptors: an intra-subject analysis[J]. Basic Clin Pharmacol Toxicol, 2019, 124(3): 245-255. DOI: 10.1111/bcpt.13137.
[32]	van Eijk M, Boosman RJ, Schinkel AH, et al. Cytochrome P450 3A4, 3A5, and 2C8 expression in breast, prostate, lung, endometrial, and ovarian tumors: relevance for resistance to taxanes[J]. Cancer Chemother Pharmacol, 2019, 84(3): 487-499. DOI: 10.1007/s00280-019-03905-3.
[33]	Kumar H, Gupta NV, Jain R, et al. A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer[J]. J Adv Res, 2023, 54: 271-292. DOI: 10.1016/j.jare.2023.02.005.
[34]	Nabekura T, Kawasaki T, Jimura M, et al. Microtubule-targeting anticancer drug eribulin induces drug efflux transporter P-glyco-protein[J]. Biochem Biophys Rep, 2020, 21: 100727. DOI: 10.1016/j.bbrep.2020.100727.
[35]	Bhagyaraj E, Ahuja N, Kumar S, et al. TGF-β induced chemoresistance in liver cancer is modulated by xenobiotic nuclear receptor PXR[J]. Cell Cycle, 2019, 18(24): 3589-3602. DOI: 10.1080/15384101.2019.1693120. pmid: 31739702
[36]	Li Y, Lin W, Chai SC, et al. Design and optimization of 1H-1,2,3-triazole-4-carboxamides as novel, potent, and selective inverse agonists and antagonists of PXR[J]. J Med Chem, 2022, 65(24): 16829-16859. DOI: 10.1021/acs.jmedchem.2c01640.
[37]	Finamore C, Festa C, Fiorillo B, et al. Expanding the library of 1,2,4-oxadiazole derivatives: discovery of new farnesoid X receptor (FXR) antagonists/pregnane X receptor (PXR) agonists[J]. Molecules, 2023, 28(6): 2840. DOI: 10.3390/molecules2806 2840.
[38]	Mustonen EK, Pantsar T, Rashidian A, et al. Target hopping from protein kinases to PXR: identification of small-molecule protein kinase inhibitors as selective modulators of pregnane X receptor from TüKIC library[J]. Cells, 2022, 11(8): 1299. DOI: 10.3390/cells11081299.