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"Tujuan: AmpIifikasi dan over-ekspresi c-erbB2 and MRP1 ditemukan pada beberapa tumor dan merupakan hal yang panting daiam menentukan perilaku karsinoma. Tujuan penelitian ini untuk mengevaluasi hubungan antara ekspresi protein c-erbB-2 dan MRPI dengan derajat keganasan karsinoma payudara duktal invasif dan respon kemoterapi neoajuvan CAF.Cara kerja: Ekspresi protein c-erB2 and MRP1 dianalisa secara imunohistokimia pada 27 blok paraffin dari pasien yang telah didiagnosa sebagai karsinoma payudara duktal. Hasilnya dihubungkan dengan derajat keganasan dan respon kemoterapi. Hubungan antara beberapa variabel dianalisa dengan uji analisa statistik non-parametrik Kendall,Hasil: Ekspresi protein C-erbB-2 positif pada 33,3 % tumor. Ekspresi protein MRP1 negatif pads 25,9 %, positif lemah pada 11,1 %, positif sedang pads 37,1 % dan positif kuat pada 25,9 %. Terdapat hubungan yang bermakna antara ekspresi protein C-erbB-2 dengan MRP1 (p=0,020, r=0,370). Tetapi, tidak ada hubungan yang bermakna antara ekspresi protein C-erbB-2 dengan derajat keganasan (p= 0,210) dan respon kemoterapineoajuvan CAF (p=0,168). Tidak ada hubungan yang bermakna antara ekspresi proteinMRPI dengan derajat keganasan (p= 0,144) dan respon kemoterapi neoajuvan CAF (p=0,056). )_ Tidak ada hubungan yang bermakna antara ekspresi protein MRP1 dengan derajat keganasan dengan respon kemoterapi neoajuvan CAF (p-,I30).Kesimpulan: Terdapat hubungan yang bermakna antara ekspresi protein c-erbB-2 dengan MRP1. Tidak ada hubungan yang bermakna antara ekspresi protein c-erbB2 dan MRPI dengan derajat keganasan dan respon kemoterapi. Tetapi, ada kecenderungan bahwa ekspresi protein MRP berhubungan searah dengan derajat keganasan dan respon kemoterapi. Tidak ada hubungan yang bermakna antara derajat keganasan dengan respon kemoterapi.

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Aims: Amplification and over-expression of c-erbB2 and MRP1 gene has been demonstrated in several tumors and thought to be important determinant of behaviors of carcinoma. In this study, correlation between c-erbB-2 and MRPI protein expression with histological grade of invasive ductal carcinoma of the breast and CAF neoadjuvant chemotherapy response were evaluated.

Methods: Paraffin-embedded tissue section from 27 patients who diagnosed as invasive ductal carcinoma of the breast were analyzed immunohistochemically for the expression of c-erbB2 and MRPI. The result was compared with histological grade and CAF neoadjuvant chemotherapy response. The correlation between several variable were analyzed by non-parametric statistical analysis correlation of Kendall.

Result: C-erbB-2 protein expression were positive in 33.3 % of the tumours. MRP1 protein expression were negative in 25.9 %, weak positive in 11.1 %, moderate positive in 37.1 % and strong positive in 25.9 %. There was significant correlation between C-erbB-2 with MRPI protein expression (p(_020, r0.370). However, there was no significant correlation between C-erbB-2 protein expression with histological grade (p= 0.210) and chemotherapy response (p=0.168). There was no significant correlation between MRP I protein expression with histological grade (p= 0.144) and chemotherapy response (p-0.056). There was no significant correlation between histological grade with chemotherapy response (p.41130).

Conclusion C-erbB-2 and MRPI protein expression were weakly correlated with each other. There was no significant correlation among both of the c-erbB2 and MRP I protein with histological grade and CAF neoadjuvant chemotherapy response_ However, there was a tendency that the expression of MRPI protein was related to histological grade and CAF neoadjuvant chemotherapy response. There was no significant correlation between histological grade and CAF neoadjuvant chemotherapy response."

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Kurkumin merupakan pigmen kuning alami dari rimpang kunyit yang diduga memiliki aktivitas kemopreventif terhadap sel kanker melalui mekanisme jalur pensinyalan apoptosis. Penelitian ini bertujuan untuk menguji hubungan kurkumin terhadap kadar protein RASSF1A,  Bax, dan aktivitas kaspase-3 dalam menunjang  mekanisme apoptosis pada sel kanker payudara CSA03, MCF-7, dan MDA-MB-468.

Penelitian eksperimen in vitro dilakukan di laboratorium terpadu Fakultas Kedokteran Universitas Indonesia Jakarta,  laboratorium terpadu Fakultas Kedokteran Universitas YARSI Jakarta, RSUPN Dr. Cipto Mangunkusumo Jakarta, serta RS Islam Jakarta tahun 2016–2018. Pemberian kurkumin terhadap sel kanker didasarkan atas perbedaan dosis dan waktu pemberian. Uji sitotoksisitas  setelah pemberian kurkumin ditentukan secara MTS.   Kadar protein RASSF1A dan Bax diuji secara ELISA. Aktivitas kaspase-3 digunakan untuk mengetahui apoptosis diuji secara flowsitometri. Selanjutnya perubahan morfologi sel diamati melalui pewarnaan acridine orange/ethidium bromide.

Pemberian kurkumin terhadap sel-sel yang diuji menunjukkan konsentrasi IC₅₀ yaitu 40,85 µg/mL pada sel CSA03; 75,73 µg/mL pada sel MCF-7; dan 380,79 µg/mL pada sel MDA-MB-468. Pemberian kurkumin menunjang mekanisme apoptosis melalui jalur RASSF1A, Bax, dan aktivitas kaspase-3 pada sel kanker payudara.

 

Kata Kunci:  Apoptosis, Bax, CSA03, kaspase-3, kurkumin,  MCF-7, MDA-MB-468, pewarnaan ganda, RASSF1A

 

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Curcumin is a natural yellow pigment from turmeric rhizome which is thought to have a chemopreventive effect on cancer through the mechanism of apoptotic signaling pathways. This study aims to examine the correlation of curcumin with protein level of RASSF1A, Bax, and caspase-3 activities in conjunction with the mechanism of apoptosis in CSA03, MCF-7, and MDA-MB-468 breast cancer cells.

In vitro experimental research was carried out at the Integrated Laboratory of Faculty of Medicine, Universitas Indonesia Jakarta; RSUPN. Dr. Cipto Mangunkusumo Jakarta; and Jakarta Islamic Hospital during 2016–2018. Curcumin was administered to the cancer cells in different doses and time. Cytotoxicity test after administration of curcumin was determined by MTS. The protein level of RASSF1A and Bax were measured by ELISA. Caspase-3 activity was used to determine apoptosis by flow cytometry. Furthermore, changes in cell morphology were observed by acridine orange/ethidium bromide staining.

The administration of curcumin to the cells showed IC50 concentrations of 40.85 µg/mL in CSA03 cells; 75.73 μg/mL in MCF-7 cells; and 380.79 µg/mL in MDA-MB-468 cells. The administration of curcumin supports the mechanism of apoptosis through the RASSF1A, Bax, and caspase-3 activity in breast cancer cells.

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