20P - The suppression of breast cancer cells growth by irinotecan loaded zinc oxide nanoparticles through E2F3/Akt/Mdm2/AR controlled apoptosis

Date 04 May 2017
Event IMPAKT 2017
Session Welcome reception and Poster Walk
Topics Anticancer agents
Breast Cancer
Therapy
Biological Therapy
Presenter Karuppaiya Vimala
Citation Annals of Oncology (2017) 28 (suppl_1): i7-i8. 10.1093/annonc/mdx137
Authors K. Vimala, S. Kannan
  • Zoology, Periyar University, 636011 - Salem/IN

Abstract

Body

Background and Aim: 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 growth of breast tumors. Cell viability and expression of apoptotic markers (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, we prepared siRNA conjugated irinotecan-ZnONPs against E2F3 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 cancer cells through activate Akt kinase and Mdm2 regulated degradation through proteasome pathway, dramatically inhibited tumor growth and significantly promote cell apoptosis. Conclusion: 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 identification

(622/PO/c/02/CPCSEA/2014)

Legal entity responsible for the study

Periyar University

Funding

UGC, India

Disclosure

All authors have declared no conflicts of interest.