INTISARI Kanker payudara merupakan salah satu penyakit dengan karakteristik kompleks, dengan kasus kematian tinggi sehingga penanganannya membutuhkan strategi yang efektif dan efisien. Kokemoterapi merupakan salah satu alternatif terapi yang menjanjikan. Penelitian ini bertujuan untuk menemukan kombinasi terapi berbasis herbal dengan doxorubicin melalui penghambatan proliferasi dan metastasis. Sebelas tanaman yang kami pilih yaitu kayu secang/SE, daun sirsak/SI, rimpang temulawak/TE, rimpang kunyit/KU, rimpang lempuyang/LE, rimpang laos/LA, daun sambung nyawa/SN, kayu manis/KM, daun awar-awar/AW, herba rumput mutiara/RM dan buah brusea/BR. Serbuk kering dimaserasi dengan etanol 96% selama 3x24 jam, diuapkan hingga diperoleh ekstrak kering. Skrining sitotoksik pada sel kanker payudara 4T1 dan MCF-7 serta sel normal fibroblast NIH-3T3 dilakukan dengan MTT assay, profil siklus sel dan induksi apoptosis dengan flow cytometry, serta antimigrasi sel 4T1 dengan wound healing assay. Skrining menghasilkan dua kandidat ekstrak yang nantinya dikombinasikan dengan doxorubicin. Nilai indeks kombinasi (CI) diperoleh dari MTT assay kombinasi dan dianalisa Compusyn software. Kombinasi sinergis diikuti profil siklus sel dan induksi apoptosis dengan flow cytometry, uji antimigrasi dengan wound healing assay, ekspresi MMP9 dengan gelatin zymograph, dan ekspresi protein PARP-1, p-I-KappaB-alfa, dan Rac1 dengan Western Blotting. Hasil skrinning sitotoksik, profil siklus sel dan induksi apoptosis menunjukkan SE sebagai ekstrak terpilih, sedangkan dari skrining antimigrasi terpilih ekstrak AW. Kombinasi SE, AW dengan doxorubicin konsentrasi 5:3:0,58 µg/ml dan 16:8:1,16 mikrogram/ml memperlihatkan efek sinergis pada sel MCF-7. Sedangkan pada sel 4T1 efek sinergis tercapai pada konsentrasi 4:0,6:0,09 mikrogram/ml, 5:0,8:0,12 mikrogram/ml dan 10:1,7:0,23 mikrogram/ml. Kombinasi SE-AW-dox konsentrasi 16:8:1,16 mikrogram/ml pada sel MCF-7 dan 10:1,7:0,23 mikrogram/ml pada sel 4T1 menghambat siklus sel di fase G2/M dan menginduksi apoptosis yang diindikasikan dengan menurunnya ekspresi PARP-1, menghambat migrasi dan ekspresi MMP9 pada sel 4T1, serta menurunkan ekspresi protein p-I-KappaB-alfa dan Rac-1. Hasil penelitian diharapkan menjadi dasar penelitian lebih lanjut dalam pengembangan terapi kanker payudara yang aplikatif, efektif, dan efisien

ABSTRACT Indonesian has potential source of various plants for the development and discovery of new therapeutic agent. Breast cancer is one of the complex diseases with high mortality cases in the world, so fighting cancer requires an effective and efficient strategy. Combination therapy with a chemopreventive agent is one of the promising alternative therapy. This study aims to find cancer therapy based on Indonesian herbal combined with doxorubicin through inhibition of proliferation and metastasis. The herbs were sappan wood/SE, annona leaves/SI, temulawak rhizome/TE, curcuma rhizome/KU, lempuyang rhizome/LE, laos rhizome/LA, sambung nyawa leaves/SN, kayu manis/KM, awar-awar leaves/AW, rumput mutiara herbs/RM and brusea fruits/BR. The 11 herbs was macerated with ethanol 96% for 3x24 hours to get dried extracts. Cytotoxic screening to 4T1 and MCF-7 breast cancer also fibroblast cells NIH-3T3 was done with MTT assay, cell cycle profile and apoptototic induction with flow cytometry, selectivity index to, and the antimigration effect to 4T1 by wound healing assay. The bioassay screening will resulted two candidate that will be combined with doxorubicin. The combination index (CI) was obtained from MTT assay combination and analyzed with Compusyn software. The synergistic combination was then followed by cell cycle profiling and apoptotic induction by flow cytometry, the antimigration effect by wound healing assay, MMP9 expression by gelatin zymography, and protein expression of PARP-1, p-I-KappaB-alfa, and Rac1 by Western Blotting. The cytotoxic screening, cell cycle profiling, and apoptotic induction showed SE as the selected extract, while the antimigration effect found AW for the chosen candidate. Combination of SE, AW with doxorubicin 5: 3: 0.58 micrograms/ml, 8: 4: 0.87 µgg/ml and 16: 8: 1.16 micrograms/ml showed a synergistic effect on MCF-7 cells. Whereas in 4T1 cells the synergistic effect was achieved at 4: 0.6: 0.09 micrograms/ml, 5: 0.8: 0.12 micrograms/ml, and 10: 1.7: 0.23 micrograms/ml. The combination of SE-AW-dox 16:8: 1.16 micrograms/ml in MCF-7 and 10:1.7:0.23 micrograms/ml in 4T1 cells inhibited cell cycle in G2/M phase, induced apoptotic cells, revealed antimigration effect, and decreased MMP9 expression. The Western blotting showed suppression of PARP-1, p-I-KappaB-alfa, and Rac-1 expression by the combination. These results were prospected for further research to attain applicable, effective, and efficient breast cancer therapy.

Kata Kunci : kanker payudara, secang, awar, doxorubicin, terapi kombinasi, sitotoksik, antimigrasi /breast cancer, sappan wood, F. septica leaves, doxorubicin, combination therapy, cytotoxic, antimigration