Abstract

Carcinoma of the cervix remains a significant health problem for women worldwide and new treatments are urgently required. In previous works we have described that the interference of Antisense non-coding mitochondrial RNA (AsncmtRNA) with antisense oligonucleotides (ASO) induces a massive cell death mediated by apoptosis in primary cultures of human advanced cervical cancer. The aim of this study was to evaluate the efficacy of the ASO treatment using patient derived xenograft (PDX) models of advanced cervical cancer. Therefore, fresh human biopsies were surgically implanted into the cervix of immuno-compromised mice (F0). One hundred days after the engrafted, tumor was harvested and fragmented to expand subcutaneously into a new group of mice, referred as F1. Animals were treated with 200 µg of AS0 1537S, every other day until complete 10 doses. Primary biopsies and tumor growth in the different generations, were HPV-genotypes by PCR and, a broad analysis of proliferation, antiapoptotic, epithelial and angiogenesis biomarkers were carried out by western blot and immunohistochemistry. The characterization of tumor samples determined the presence of HPV 16 and no changes in expression of Cytokeratin 17, PCNA and Ki67 were observed through the different generations. The evaluation of the ASO therapy do not show a delay on tumor growth but shows an important inhibition of the metastatic spread, associated with a drop in the expression of Survivin, Rac and Bcl-xL. Grants: FONDEF D10E1090 and CCTE-PFB16. CONICYT.