รหัสดีโอไอ 10.14456/ijps.2019.26
Creator Thongtham Suksawat
Title Effects of rifampicin on the expressions of drug transporter OATP1B1, drug metabolizing enzymes CYP3A4 and CYP3A5, and nuclear receptors PXR and AhR in human HepG2 and BeWo cells
Contributor Kanokwan Jarukamjorn, Waranya Chatuphonprasert
Publisher Faculty of Pharmaceutical Sciences KKU MSU UBU
Publication Year 2019
Journal Title Isan Journal of Pharmaceutical Sciences
Journal Vol. 15
Journal No. 2
Page no. 118-128
Keyword rifampicin, hepatocellular carcinoma, choriocarcinoma, cytochrome P450, drug transporter, nuclear receptor
URL Website https://tci-thaijo.org/index.php/IJPS
Website title Isan Journal ofPharmaceutical Sciences; IJPS
ISSN 19050852
Abstract Rifampicin, an anti-tuberculosis drug, has been extensively reported for drug interaction due to its ability to induce several metabolizing enzymes. Drug transporter OATP1B1, drug metabolizing enzymes CYP3A4 and CYP3A5, and nuclear receptors PXR and AhR, are involved in metabolism of a clinical drug, especially in hepatocytes. However, the information of rifampicin on those genes in human placenta is still less. This study aimed to investigate the effects of rifampicin on the expressions of OATP1B1, CYP3A4 CYP3A5, PXR and AhR, in hepatocellular carcinoma (HepG2) and choriocarcinoma (BeWo) cells. Materials and method: HepG2 and BeWo cells (5x105 cells per well) were cultured in DMEM with 10% FBS and incubated with rifampicin at the final concentrations of 0.5, 5 and 10 ?M for 24 hours. Total RNAs were extracted and the mRNA expression of each gene was determined by RT-qPCR. Results: Rifampicin induced the expression of CYP3A4 and CYP3A5 mRNA in both HepG2 and BeWo cells for 4-6 fold. Likewise, the levels of OATP1B1 mRNA were significantly elevated by rifampicin, compared to control group, in both HepG2 (18-23 fold) and BeWo (2-4 fold). However, rifampicin did not modify the expression of PXR in HepG2 while it extensively suppressed the PXR mRNA in BeWo. On the other hand, the expression of AhR was significantly induced by rifampicin in HepG2 but not in BeWo, only rifampicin at the lowest concentration test (0.5 ?M) down-regulated the AhR mRNA expression (p-value < 0.05). Conclusion: The regulatory mechanism of rifampicin was different between HepG2 and BeWo cells. Rifampicin up-regulated the expression of OATP1B1, CYP3A4 and CYP3A5 in HepG2 cells, at least in part, via the AhR pathway. However, the expressions of OATP1B1, CYP3A4 and CYP3A5 in BeWo cells might be regulated by other receptors, beside PXR and AhR.
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บรรณานุกรม

Thongtham Suksawat,Kanokwan Jarukamjorn; Waranya Chatuphonprasert. (2019) Effects of rifampicin on the expressions of drug transporter OATP1B1, drug metabolizing enzymes CYP3A4 and CYP3A5, and nuclear receptors PXR and AhR in human HepG2 and BeWo cells. Isan Journal of Pharmaceutical Sciences,15,118-128.
Thongtham Suksawat,Kanokwan Jarukamjorn; Waranya Chatuphonprasert. "Effects of rifampicin on the expressions of drug transporter OATP1B1, drug metabolizing enzymes CYP3A4 and CYP3A5, and nuclear receptors PXR and AhR in human HepG2 and BeWo cells". Isan Journal of Pharmaceutical Sciences 15 (2019):118-128.
Thongtham Suksawat,Kanokwan Jarukamjorn; Waranya Chatuphonprasert. Effects of rifampicin on the expressions of drug transporter OATP1B1, drug metabolizing enzymes CYP3A4 and CYP3A5, and nuclear receptors PXR and AhR in human HepG2 and BeWo cells. Faculty of Pharmaceutical Sciences KKU MSU UBU:ม.ป.ท. 2019.