الفهرس 
breast cancerOnly 14 pages are availabe for public view
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Abstract
Summary and conclusions
The combination of herceptin with conventional chemotherapies greatly improved the responses and prolonged the survival rates but it is frequently associated with intolerable side effects particularly cardiac adverse effects. These drawbacks stimulated us to investigate the use of new, less toxic agents with potential chemoprotective effects such as, resveratrol and didox as potential adjuvant therapy combined with herceptin.
The viability (SRB) assay was carried out to investigate the effect of resveratrol (RES) and didox (DID) on herceptin (HER) induced cytotoxicity
against two breast cancer cell lines, namely; T47D and MCF-7 cells. Then, a set of experiments was designed to investigate the possible underlying mechanisms. These experiments included the detection of proapoptotic (Bax), and the anti-apoptotic (Bcl-2 and Bcl-xl) genes expression using PCR technique. The expression of HER-2 receptor was determined by immune-cytochemical staining technique. The activity of caspase-3, which plays a central role in the execution-phase of cell apoptosis, was detected. Finally, the effect of HER, RES, DID and their combination on cell cycle distribution was assessed using DNA flow-cytometry.
The results of the current study were as follows:
1- Both RES and DID had a synergistic effect on HER induced cytotoxicity in T47D and MCF-7 cell lines.
2- In T47D cells the combination of HER with RES or DID significantly decreased the expression of Bcl-xl gene, while no apparent change in the Bax gene expression was produced by both combinations and only HER/DID combination significantly decreased the Bcl-2 gene expression compared to single HER treatment group.
3- In MCF-7 cells both HER/RES and HER/DID combinations markedly increased the expression of Bax gene and decreased the expression of Bcl-2 gene while Bcl-xl gene expression remains unaffected compared to single HER treatment group.
4- The combination of RES and DID with HER apparently decreased the activity of caspase-3 enzyme compared to single HER treatment group in T47D cells.
5- HER-2 receptor expression was significantly decreased following the combination of RES with HER while HER/DID combination didn’t affect the HER-2 receptor expression compared to single HER treatment group in T47D cells.
6- In bothT47D and MCF-7 cells, HER/RES combination produced a significant increase of the cells in the late apoptotic cell phase (pre-G) due to cell cycle arrest at the S-phase compared to single HER treatment group , while HER/DID combination didn’t produce similar effect .
Conclusions:
Both RES and DID synergistically interact with HER in T47D and MCF-7 breast cancer cell lines and this synergism is not restricted to HER-2 overexpressing breast cancer cells.
Recommendations:
The combinations of RES or DID with HER are recommended to be further studied both in-vivo and clinically to confirm our results.