Kanker payudara masih menjadi masalah kesehatan global. Modalitas terapi yang digunakan untuk pasien kanker payudara diataranya agen kemoterapi doksorubisin (DOX). DOX digunakan untuk pengobatan kanker dengan mekanisme interkalasi DNA dan penghambatan topoisomerase II, serta penggunaannya mengalami resistensi. Bahan alam berpotensi digunakan untuk terapi kombinasi mengatasi resistensi doksorubisin. Bahan alam yang digunakan diantaranya dari jahe merah yang mengandung 6-shogaol. Senyawa 6-Shogaol sebagai agen kemoterapi yang meregulasi ekspresi gen yang berhubungan dengan proses proliferasi sel. Pada penelitian ini dilakukan analisis ekspresi gen pada basis data Gene Expression Omnibus (GEO) terkait pengobatan doksorubisin (GSE124597) dan pemberian 6-shogaol (GSE36973) dengan tujuan mengetahui perbandingan pola ekspresi gen yang dipengaruhi keduanya terhadap sel kanker payudara MCF7. Dilakukan juga anotasi fungsi gen yang diekspresikan menggunakan Gen Ontologi (GO) dan KEGG, jejaring farmakologi menggunakan basis data STITCH, serta simulasi penambatan molekuler untuk mengetahui mekanisme kerja antikanker. Sifat antikanker doksorubisin, 6-shogaol, dan ekstrak jahe merah kemudian dikonfirmasi secara invitro meggunakan metode MTT. Hasil analisis Diffrential Expression Genes (DEG) menghasilkan 227 DEG yang sama (DEG bersama) akibat pemberian doksorubisin dan 6-shogaol. Hasil anotasi fungsi gen dengan GO menunjukkan dari 227 DEG terkait dengan proliferasi sel melalui jalur TP53.Demikian juga terkait hasil analisis jejaring farmakologi menunjukkan doksorubisin dan 6-shogaol terhubung dengan protein TP53. Hasil analisis interaksi protein-protein (PPi) menunjukkan jalur persinyalan TP53 terhubung dengan protein CDKN1A, GADD45A, DDIT3 dan CXCL12. Penambatan molekuler senyawa doksorubisin dan 6-shogaol pada protein TP53 menghasilkan energi ikatan berturut-turut -7.97 kcal/mol dan -6.05 kcal/mol. Nilai IC50 senyawa doksorubisin, 6-shogaol, dan ekstrak jahe pada sel MCF-7 berturut-turut adalah: 15.45 µg/ml, 61.24 µg/ml dan 144.99 µg/ml. Hal ini menunjukkan 6-shogaol dapat digunakan sebagai kandidat komplementer antikanker pada sel MCF-7.
Breast cancer is still a global health problem. Therapeutic modalities used for breast cancer patients include the chemotherapeutic agent doxorubicin (DOX). DOX is used for the treatment of cancer with DNA intercalation mechanisms and topoisomerase II inhibition, and its use has experienced resistance, so a combination therapy of natural ingredients is needed. The natural ingredients used include red ginger which contains 6-shogaol. 6-Shogaol compound as a chemotherapeutic agent that regulates gene expression related to cell proliferation processes. In this study, gene expression analysis was carried out on the Gene Expression Omnibus (GEO) database related to doxorubicin treatment (GSE124597) and 6-shogaol administration (GSE36973) with the aim of knowing a comparison of gene expression patterns affected by both of them on MCF7 breast cancer cells. Functional annotations of expressed genes were also performed using Gene Ontology (GO) and KEGG, pharmacological networks using the STITCH database, as well as molecular docking simulations to determine the mechanism of anticancer action. The anticancer properties of doxorubicin, 6-shogaol, and red ginger extract were then confirmed in vitro using the MTT method. The results of the Differential Expression Genes (DEG) analysis yielded the same 227 DEGs as a result of doxorubicin and 6-shogaol administration. The results of gene function annotations with GO showed that 227 DEGs were related to cell proliferation through the TP53 pathway. Likewise, the results of pharmacological network analysis showed that doxorubicin and 6-shogaol were linked to the TP53 protein. The results of protein-protein interaction (PPi) analysis showed that the TP53 signaling pathway was connected to the CDKN1A, GADD45A, DDIT3 and CXCL12 proteins. Molecular docking of the compounds doxorubicin and 6-shogaol to the TP53 protein produces a binding energy of -7.97 kcal/mol and -6.05 kcal/mol, respectively. The IC50 values ââof doxorubicin, 6-shogaol, and ginger extract in MCF-7 cells were: 15.45 µg/ml, 61.24 µg/ml and 144.99 µg/ml, respectively. This shows that 6-shogaol can be used as a complementary anticancer candidate in MCF-7 cells. |
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