Abstract
The purpose of this study is to investigate the combined effects of exemestane and aspirin on MCF-7 human breast cancer cells. Antiproliferative effects of exemestane and aspirin, alone and in combination, on growth of MCF-7 human breast cancer cells were assessed using the MTT assay. Synergistic interaction between the two drugs was evaluated in vitro using the combination index (CI) method. The cell cycle distribution was analyzed by flow cytometry and Western blotting was used to investigate the expression of cyclooxygenase-1, cyclooxygenase-2 and Bcl-2. MTT assays indicated that combination treatment obviously decreased the viability of MCF-7 human breast cancer cells compared to individual drug treatment (CI<1). In addition, the combination of exemestane and aspirin exhibited a synergistic inhibition of cell proliferation, significantly arrested the cell cycle in the G0/G1 phase and produced a stronger inhibitory effect on COX-1 and Bcl-2 expression than control or individual drug treatment. These results indicate that the combination of exemestane and aspirin might become a useful method to the treatment of hormone- dependent breast cancer. The combination of the two inhibitors significantly increased the response as compared to single agent treatment, suggesting that combination treatment could become a highly effective approach for breast cancer.
Highlights
Breast cancer is the leading cause of cancer death in females worldwide, accounting for 23% of the total new cancer cases and 14% of the total cancer deaths(Jemal et al, 2011)
The combination of exemestane with aspirin for 72 h resulted in a synergistic effect (CI < 1) on the inhibition of the growth of MCF-7 cells when combination index (CI) is between 0.47 and aspirin
Our results clearly indicated that both as positive control. (b) Media was collected from the different treatment groups and prepared for use in the EIA assay for prostaglandin E2 (PGE2)
Summary
Breast cancer is the leading cause of cancer death in females worldwide, accounting for 23% of the total new cancer cases and 14% of the total cancer deaths(Jemal et al, 2011). 75% of all patients with breast cancer have a tumor expressing the estrogen receptor (ER) and/or the progesterone receptor. Over the last few years ,aromatase inhibitors (AIs) have proved to be effective treatment for ER positive breast cancer. AIs have been used as the standard first-line treatment for patients with advanced estrogen dependent breast cancer (Smith and Dowsett 2003; Geisler and Lonning 2005; Riemsma et al, 2010). Cyclooxygenases (COX)-1 and COX-2 have been found to be over-expressed in breast cancer tissue when compared to normal tissue (Hwang et al, 1998). COX-1 and COX-2 have been causally linked to breast cancer cell proliferation, motility and invasiveness (Timoshenko et al, 2003; Basu et al, 2006; Hiraga et al, 2006; Tsatsanis et al, 2006). PGE2 have many effects, such as induction of Bcl-2 (which has a role in inhibition of apoptosis) (Sheng et al, 1998), influencing estrogen biosynthesis by induction of the aromatase gene (Harris et al, 1999), and involvement in angiogenesis (Gately, 2000)
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