ABSTRAK
Penurunan sensitivitas hingga resistensi terhadap tamoksifen sering terjadi dalampengobatan kanker payudara jangka panjang. Salah satu penyebab utamanya adalahpeningkatan ekspresi transporter efluks P-glikoprotein (P-gp) dan Breast CancerResistance Protein (BCRP). Kurkumin diketahui sebagai penghambat P-gp danBCRP. Pemberian kurkumin pada sel yang telah menurun sensitivitasnya terhadaptamoksifen diharapkan mampu meningkatkan sensitivitas sel kanker payudaraterhadap tamoksifen melalui penghambatan kedua transporter tersebut.MetodeSel MCF-7 dipaparkan tamoksifen 1 µM selama 10 pasasi (sel MCF-7(T)),kemudian dianalisis perubahan sensitivitas sel terhadap tamoksifen melaluiviabilitas sel dan ekspresi mRNA P-gp dan BCRP. Pada sel MCF-7(T), kurkumindiberikan dalam dosis 5, 10, dan 20 µM dengan atau tanpa tamoksifen selama 5 haridan dianalisis viabilitas sel dan ekspresi mRNA P-gp dan BCRP pada hari ke-2 dan5. Sebagai kontrol positif, verapamil 50 µM digunakan sebagai penghambat P-gp,ritonavir 15 µM dan nelfinavir 15 µM sebagai penghambat BCRP.HasilSetelah diberikan tamoksifen 1 µM selama 10 pasasi (44 hari), sel MCF-7(T)menurun sensitivitasnya terhadap tamoksifen yang dibuktikan dengan terjadinyapergeseran CC50 sebesar 32,08 kali, peningkatan viabilitas sel sebesar 106,4%, danpeningkatan ekspresi mRNA P-gp dan BCRP sebesar 10,82 kali dan 4,04 kali.Pemberian kurkumin dengan atau tanpa tamoksifen selama 5 hari dapatmenurunkan viabilitas sel dan ekspresi mRNA P-gp dan BCRP (p < 0,05).KesimpulanKurkumin meningkatkan sensitivitas sel MCF-7(T) terhadap tamoksifen yangditandai dengan penurunan viabilitas sel dan ekspresi mRNA P-gp dan BCRP.Peningkatan sensitivitas tersebut diduga terjadi melalui penghambatan ekspresimRNA P-gp dan BCRP oleh kurkumin.
ABSTRACT
BackgroundDecrease of sensitivity or resistance to tamoxifen occurs after long-term treatmentin breast cancer. One of the major factor in tamoxifen resistance is overexpressionof efflux transporter P-glycoprotein (P-gp) and Breast Cancer Resistance Protein(BCRP). Curcumin has been known as inhibitor of P-gp and BCRP. The addition ofcurcumin to tamoxifen resistant cells is expected to increase the sensitivity of breastcancer cells to tamoxifen.MethodsMCF-7 breast cancer cell line was exposed with tamoxifen 1 µM for 10 passage(MCF-7(T)), then cell viability and mRNA expression of P-gp and BCRP wereanalyzed. To the MCF-7(T) cells, curcumin of 5, 10, dan 20 µM with or withouttamoxifen was given for 5 days and cell viability and mRNA expression of P-gpand BCRP were analyzed on day 2 and 5. As positive control, verapamil 50 µM wasused as P-gp inhibitor, ritonavir 15 µM and nelfinavir 15 µM were used as BCRPinhibitor.ResultsThe administration of tamoxifen 1 µM for 10 passage (44 days), caused a decreasedof MCF-7(T) cells sensitivity to the drug, with 32,08 times reduction in CC50towards tamoxifen, increased of cell viability of 106,4%, and increased mRNAexpression of P-gp and BCRP mRNA of 10,82 and 4,04 fold, respectively. Theadministration of curcumin with or without tamoxifen for 5 days reduced cellviability and the mRNA expression of P-gp mRNA and BCRP (p < 0,05).ConclusionCurcumin increased MCF-7(T) sensitivity to tamoxifen, characterized by decreasedof cell viability and mRNA expression of P-gp and BCRP. Increased of sensitivitywas estimated at least in part through inhibition of P-gp and BCRP mRNAexpression by curcumin. |
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