Coelomic Fluid of Eisenia fetida Ameliorates Cetuximab to Reduce K-Ras and Vimentin Expression through Promoting RUNX3 in an AOM/DSS-Induced Colitis Associated Colon Cancer

Sofy Permana; Reyudzky Putri Fityanti; Eviana Norahmawati; Agustin Iskandar; Erika Desy Anggraini Mulyadi; Agustina Tri Endharti

doi:10.1155/2020/9418520

Coelomic Fluid of Eisenia fetida Ameliorates Cetuximab to Reduce K-Ras and Vimentin Expression through Promoting RUNX3 in an AOM/DSS-Induced Colitis Associated Colon Cancer

Evid Based Complement Alternat Med. 2020 Jul 19:2020:9418520. doi: 10.1155/2020/9418520. eCollection 2020.

Authors

Sofy Permana¹, Reyudzky Putri Fityanti², Eviana Norahmawati³, Agustin Iskandar⁴, Erika Desy Anggraini Mulyadi⁵, Agustina Tri Endharti^{4

6}

Affiliations

¹ Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia.
² Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
³ Department of Pathology Anatomy, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
⁴ Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
⁵ Undergraduate Program of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia.
⁶ Biomedical Central Laboratory, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

Abstract

Ulcerative colitis is a major risk factor that increases the occurrence of colorectal cancer. In colorectal cancer due to colitis, intestinal inflammation plays an important role which causes DNA damage. The aim of this study is to investigate the anticancer effect of coelomic fluid of Eisenia fetida (CFEF) and cetuximab combinations. Colitis associated colon cancer was induced in BALB/c mice by DSS/AOM. The mice were randomly divided into six groups: group 1 received vehicle (control), groups 2-6 received DSS/AOM, groups 3-5 received cetuximab + CFEF (30, 60, or 120 mg/kgBW), and group 6 received CFEF only. After the 12^th week of treatments, the colon tissues were removed for histological examination and immune-fluorescence. Intestinal Epithelial Cells (CECs) were analyzed by flow cytometer. Administration of CFEF significantly decreased the severity of DSS/AOM-induced CAC in a dose-dependent manner. The combinations of CFEF-cetuximab were revealed by histological change. The CFEF significantly reduced the severity scores (P < 0.05). The combinations of CFEF-cetuximab significantly inhibited K-Ras and vimentin expressions, whereas the percentage of RUNX3 significantly increased in CECs. The increasing of RUNX3 could prevent EMT, so that it can decrease K-Ras and vimentin to suppressed cell invasion and migration by CFEF. Our results suggest that CFEF has the therapeutic potential to CAC.