الفهرس 
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Abstract
Breast cancer is the second most common cancer in the world and, by far the most frequent cancer among women. Hormonal therapy is a mainstay in the clinical management of patients with breast tumors that express estrogen receptor (ER). The antitumor efficacy of these endocrine treatments depends on tight regulation of breast tumor cell growth by estrogens and growth factors.
However, as these cancers progress, they usually become resistant to antiestrogens, and most patients no longer respond to endocrine therapy. New options for antiestrogen treatment are urgently needed to enhance patient survival and quality of life.
The aim of this study is to determine and evaluate the impact of re-expressing estrogen receptor beta through demethylating agents as 5-Aza-2′-deoxycytidine (Decitabine) pre-treatment on two different breast cancer cell lines MCF-7 (4OHT sensitive) and LCC-2 (4OHT resistant) in the presence or absence of either tamoxifen or raloxifene which are both selective estrogen receptor modulators (SERMs).
In the present study, in order to determine the possible anti-tumor effects of these drugs,the level of expression and the activity of the following parameters; ERα, ER-β, Caspase-3, beta-catenin, Cyclin-D1, HER-2 and IGF-1 was determined in order to invent new strategies for controlling the progression and proliferation of breast cancer through the implication of new treatment combinations still including the old classical drugs.
Experimental cultures were assigned to six groups, group I included MCF-7 & LCC-2 cells left untreated and serve as negative controls.group II included MCF-7 and LCC-2 cells treated with 20μmol tamoxifen in DMSO at a final concentration of 1% v/v of culture media. group III included MCF-7 and LCC-2 treated with 50μmol raloxifene in DMSO at a final concentration 1% v/v of culture media. group IV included MCF-7 and LCC-2 treated with 15μmol decitabine in DMSO at a final concentration of 1% v/v of culture media. group V included MCF-7 and LCC2 treated with 20μmol tamoxifen and 15μmol decitabine in DMSO at a final concentration of 1% v/v of culture media. group VI included MCF-7 and LCC-2 treated with 50μmol raloxifene and 15μmol decitabine in DMSO at a final concentration of 1% v/v of culture media.
Results of the current study have revealed that the addition of demethylating agent 5-Aza-2′-deoxycytidine to either tamoxifen or raloxifene in both cell line models (MCF-7 and LCC-2) have resulted in either improvement or deterioration of different pathwayswhen compared to either the control group or the group treated with any of the two drugs alone,
Thus, it has been found that for example, ER-beta and ER-alpha expression level, in addition to casapase-3 activity, all of them were significantly improved (increased) when demethylating agent 5-Aza-2′-deoxycytidine was added to either tamoxifen or raloxifene, or at least in some cases they were non-significantly altered (not decreased), while cyclin D-1 and beta-catenin pathways were obviously impaired (increased) in both cell lines MCF-7 and LCC-2.
In regard to HER-2 and IGF-1pathways there was obvious improvement (decrease) in LCC-2 cell line when 5-Aza-2′-deoxycytidine was added to either tamoxifen or raloxifene, while in MCF-7 cell line the addition of 5-Aza-2′-deoxycytidine to any of the two drugs have led to the deteriorationor even the corruption of both pathways, which means that the level of expression of both proteins has been clearly unregulated leading to more resistance towards endocrine or anti-hormonal therapy.
However, it has been found that ER-β expression in breast tumors varies widely and attempts to correlate ER-β with various biomarkers have resulted in varied, often contradictory conclusions.
Hence, it is worth to say that the mainpoints discussed in the presentstudy are still under research and may need furtherinvestigations in the future which may be done either by using different therapeutic regimens, using more specific ER-β expressing agent or by just tailoring different concentrations of the same drugs used in the current study. Moreover, if the current study could be extended to include some clinical trials in the future, this would have more positive impact on the efficacy of treatment.