| dc.description.abstract | According to studies in some aspects of cancer therapy and diagnosis, breast cancer seems to unquestionably necessitate implementation of novel therapeutics. It is obvious that clarification of molecular pathogenesis is an essential part of these efforts. Among important biomolecules, the epidermal growth factor receptors (EGFR) have been shown to be over activated in breast cancer. Additionally, gap junctions play an important role in the cell proliferation. However, there are controversial issues about their role in cancer pathogenesis. Therefore, in the current investigation, Carbenoxolone (CBX) as a gap junction blocker in association with anti-EGFR antisense were used in two breast cancer cell lines and transcriptomics assessment was performed in mRNA level. Methods MCF7 and BT20 cell lines were cultivated, and were treated with different doses of CBX in association with an antisense oligonucleotide against EGFR biomolecule. Cellular cytotoxicity and growth inhibition evaluation were examined using MTT assay and Trypan blue exclusion dye tests. Gene expression profiling was carried out using DNA microarray technology and real time polymerase chain reaction was performed for data confirming. Finally, online ontology of noticeable altered genes was performed using EASE software. Results Cells were significantly affected by treatments in a time and dose dependent manner especially after 24 hour of incubation time in cell cytotoxicity assays. In MCF7 cells, 162 genes were up regulated and 161 genes were down regulated significantly. In the case of BT20 cells, it was 130 cases for up regulated genes and 177 cases for down regulated genes. Despite miscellaneous level of gene expression, it is obvious that some growth stimulating genes like IL2RA, TNFSF13b, PDGFA, LCCP1, AKT1, STAT5, EGFR and BCL2 were down regulated and in contrast some anti-proliferation related genes like TNFAIP3 was up regulated in MCF7 cells after treatments. In the case of BT20 cells, the story is repeated in the same pattern but it is mediated by other genes like IL24 gene up regulation and CTSK gene down regulation, which implies exaggerated anticancer effect of CBX in EGFR knockout cells. Discussion Based upon this investigation, it can be concluded that CBX was able to improve anti-EGFR antisense effects on both low and high proliferative types of breast cancer cell lines. Disproportionate regulation of both pre- and anti-apoptotic genes may be related to interacting biomolecules, perhaps via gap junctions as well as glucocorticoid induced apoptosis. | |
