The Bcl-2 silencing with an Antisense Oligonucleotide: Increase early Apoptosis

Abstract Background Breast cancer is a heterogenic disease and hormone dependence. Estrogen receptor is positive in more than seventy percent of breast cancer patients. Tamoxifen is an estrogen receptor (ER) antagonist and used as the first line of treatment. Drug resistance is a main reason in failure of cancer treatment and progression of the disease. Combination drug therapy is a method to treatment but is not sufficient. New approaches like molecular therapy reveal new insight to cancer therapy. Studies shown, Bcl-2 gene family inhibitors and ER blockers enhance recovery. Interfering molecules such as antisense can inhibit the expression of Bcl-2 and push the cancer cells to apoptosis. Nevertheless, their effectiveness is low, mostly due to their direct use. Methods Our team designed an Antisense Oligonucleotides (ASO). The MCF-7 and the MDA-MB-231breast cancer cell lines used to evaluate cellular proliferation. Liposome and cationic nano-complex (Niosome) used to increase cellular delivery of ASO and Tamoxifen. We also investigated the cytotoxicity and apoptotic effects of Tamoxifen, naked ASO and Nano-packed ASO. Results The ASO functional potency to assess apoptosis and expression of Bcl-2 mRNA compared in different groups. The results indicated, significant down regulation of Bcl-2 gene and inhibition of MCF-7 and MDA-MB-231 cellular proliferation. Flow-cytometry showed early apoptosis in all groups. Conclusions The ASO reduced the expression of Bcl-2 gene. It also had the synergistic effect with the Tamoxifen. In all studied groups, it was able to push cancer cells to apoptosis. The cationic nano-complex (Niosome) was more efficient than the liposome in delivering designed oligo antisense Bcl-2 into the cancer cells.