Induced By Antisense Bcl-2 In Human Neuroblastoma Cell Line Sk-n-mc Reversal Of The Malignant Phenotype Of Molecular Pathology And Proteomics Research

Neuroblastoma is a malignant childhood tumor of migrating neuroectodermal cells derived from the neural crest and destined for the adrenal medulla and the sympathetic nervous system. Tumorigenesis of neuroblastoma involves multiple genetic changes such as the activation of proto-oncogenes, inactivation of tumor suppressor genes and alterations of gene expression during the process of neuroblast differentiation. Apoptosis inhibitor bcl-2 is one of the oncogenes that closely related to the malignant transformation and progression of neuroblastoma. bcl-2 encodes a 26kDa protein that is mainly located on the outer membranes of mitochondrion, endoplasmic reticulum and nuclear. The protein Bcl-2 could inhibit the release of cytochrome c from mitochondrion and thereby block the downstream apoptosis signaling pathway. In most neuroblastoma cell lines and primary tumors, Bcl-2 is highly expressed. And it has been confirmed that Bcl-2 expression is strongly correlated with aggressive behavior and poor prognosis of neuroblastoma. Thus, Bcl-2 is proposed to be a contributor to the tumorigenesis of neuroblastoma.Recent progress made in molecular biology has led to the development of genetic therapy. Major efforts in the field can be summarized in two general approaches: gene therapy and antisense therapy. The second is to deliver to the target cells antisense molecules that target to mRNA with which they can hybridize and specifically inhibit the expression of pathogenic genes, bcl-2, the well-known apoptosis suppressor oncogene, has gained great interest in this area. It was reported that antisense oligonucleotides therapies directed bcl-2 could effectively inhibit bcl-2 expression and enhance the sensitivity to chemotherapy in various tumor cells that included hematological malignancies, prostate cancer and ovarian cancer cells. In our previous study, transfection of antisense bcl-2 sequence into human neuroblastoma cell line SK-N-MC effectively inhibited the growth of tumor cells and reduced the ability of tumor formation in nude mice. These results support...