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ABSTRAKPenurunan sensitivitas hingga resistensi terhadap tamoksifen sering terjadi dalam
pengobatan kanker payudara jangka panjang. Salah satu penyebab utamanya adalah
peningkatan ekspresi transporter efluks P-glikoprotein (P-gp) dan Breast Cancer
Resistance Protein (BCRP). Kurkumin diketahui sebagai penghambat P-gp dan
BCRP. Pemberian kurkumin pada sel yang telah menurun sensitivitasnya terhadap
tamoksifen diharapkan mampu meningkatkan sensitivitas sel kanker payudara
terhadap tamoksifen melalui penghambatan kedua transporter tersebut.
Metode
Sel MCF-7 dipaparkan tamoksifen 1 µM selama 10 pasasi (sel MCF-7(T)),
kemudian dianalisis perubahan sensitivitas sel terhadap tamoksifen melalui
viabilitas sel dan ekspresi mRNA P-gp dan BCRP. Pada sel MCF-7(T), kurkumin
diberikan dalam dosis 5, 10, dan 20 µM dengan atau tanpa tamoksifen selama 5 hari
dan dianalisis viabilitas sel dan ekspresi mRNA P-gp dan BCRP pada hari ke-2 dan
5. Sebagai kontrol positif, verapamil 50 µM digunakan sebagai penghambat P-gp,
ritonavir 15 µM dan nelfinavir 15 µM sebagai penghambat BCRP.
Hasil
Setelah diberikan tamoksifen 1 µM selama 10 pasasi (44 hari), sel MCF-7(T)
menurun sensitivitasnya terhadap tamoksifen yang dibuktikan dengan terjadinya
pergeseran CC50 sebesar 32,08 kali, peningkatan viabilitas sel sebesar 106,4%, dan
peningkatan ekspresi mRNA P-gp dan BCRP sebesar 10,82 kali dan 4,04 kali.
Pemberian kurkumin dengan atau tanpa tamoksifen selama 5 hari dapat
menurunkan viabilitas sel dan ekspresi mRNA P-gp dan BCRP (p < 0,05).Kesimpulan
Kurkumin meningkatkan sensitivitas sel MCF-7(T) terhadap tamoksifen yang
ditandai dengan penurunan viabilitas sel dan ekspresi mRNA P-gp dan BCRP.
Peningkatan sensitivitas tersebut diduga terjadi melalui penghambatan ekspresi
mRNA P-gp dan BCRP oleh kurkumin.
ABSTRACTBackground
Decrease of sensitivity or resistance to tamoxifen occurs after long-term treatment
in breast cancer. One of the major factor in tamoxifen resistance is overexpression
of 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 of
curcumin to tamoxifen resistant cells is expected to increase the sensitivity of breast
cancer cells to tamoxifen.
Methods
MCF-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 were
analyzed. To the MCF-7(T) cells, curcumin of 5, 10, dan 20 µM with or without
tamoxifen was given for 5 days and cell viability and mRNA expression of P-gp
and BCRP were analyzed on day 2 and 5. As positive control, verapamil 50 µM was
used as P-gp inhibitor, ritonavir 15 µM and nelfinavir 15 µM were used as BCRP
inhibitor.
Results
The administration of tamoxifen 1 µM for 10 passage (44 days), caused a decreased
of MCF-7(T) cells sensitivity to the drug, with 32,08 times reduction in CC50
towards tamoxifen, increased of cell viability of 106,4%, and increased mRNA
expression of P-gp and BCRP mRNA of 10,82 and 4,04 fold, respectively. The
administration of curcumin with or without tamoxifen for 5 days reduced cell
viability and the mRNA expression of P-gp mRNA and BCRP (p < 0,05).Conclusion
Curcumin increased MCF-7(T) sensitivity to tamoxifen, characterized by decreased
of cell viability and mRNA expression of P-gp and BCRP. Increased of sensitivity
was estimated at least in part through inhibition of P-gp and BCRP mRNA
expression by curcumin. "
