129P Inhibition of breast cancer cell explosion rate by irinotecan loaded zinc oxide nanoparticles through E2F3/Akt signaling circuits: A milestone in cancer gene therapy

Abstract

Background The E2F3 transcription factor claims its role in controlling cell cycle progression. Accordingly, the present investigation has been designed to assess to what extent E2F3 would be overexpressed in breast cancer. Although chemotherapeutic drugs are widely applied for clinic tumor treatment, severe toxicity restricts their therapeutic efficacy. The present study was to emphasize that the synthesis of stable SiRNA (E2F3) conjugated irinotecan loaded Zinc Oxide Nanoparticles (SiRNA- irinotecan-ZnONPs) and the elucidation of their mechanism of action in preventing the growthofbreasttumors.Cellviabilityandexpressionofapoptoticmarkers(p58,Bax, and cytochrome c) were assessed and the level of E2F3 is increased in breast cancer and highlights the efficacy of siRNA targeted to E2F3. Methods We used the green-bio method to synthesize SiRNA-irinotecan-ZnO nano complex for its use as a cancer-targeted drug delivery system to achieve enhanced cellular uptake and anticancer efficacy. To investigate the expression level of E2F3/Akt/ Mdm2/AR by RT-PCR and Western blotting analysis was carried out. Results Here, weprepared siRNA conjugated irinotecan-ZnONPs againstE2F3 significantly blocked the expression of the E2F3 in breast cancer and investigated its inherent anticancer mechanisms. We found SiRNA-irinotecan-ZnONPs inhibit growth of breast LNCaP cancer cells through activate Akt kinase and Mdm2 regulated degradation through proteasome pathway, dramatically inhibited tumor growth and significantly promote cell apoptosis. Conclusions This in vitro and in vivo study demonstrates that E2F3 is a newly identified diagnostic and potential therapeutic target in breast cancer. Outcomes of this study affirm that SiRNA-irinotecan-ZnONPs for E2F3 facilitates the silencing of E2F3 overexpression and fights against breast cancer cells growth. These findings suggested that SiRNA-irinotecan-ZnONPs were deemed as a potential drug nanocarrier for cancer therapy and opens a new path for synergistic treating of cancer with higher efficacy and decreased side effects. Clinical trial indentification In this study were approved by the Institutional Animal Ethical Committee of the Sankaralingam Bhuvaneshwai College of Pharmacy (622/PO/ c/02/CPCSEA/2014) in accordance with the policie established in the Guide to Care & Use of Experimental Animals prepared by the Committee. Legal entity responsible for the study N/A Funding PDFWM-UGC, New Delhi, India Disclosure All authors have declared no conflicts of interest.