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Azacytidine pretreatment induces chemosensitivity in MCF7 breast cancer cells to doxorubicin
- 언어ENG
- URLhttps://db.koreascholar.com/Article/Detail/355382
Chemoresistance is one of the main problems to treat different kinds of cancers or cancer cells. Therefore, it is necessary to find out the strategies to make the cancer cells sensitive to chemotherapy along with optimal dosage of drugs. We examined sensitivity of MCF7 cells through pretreating with an epigenetic modulator, azacytidine (AzaC) to doxorubicin (Dox). The cells were treated with 5 and 10 mM of AzaC for a week, subsequently with 50, 100 and 500 nM of doxorubicin for 24 and 48h. It was found that pretreatment of AzaC significantly enhance the sensitivity of MCF7 cells to Dox, inducing cell death. After 24h 15% cells underwent apoptosis in 500 nM dox treatment group while 23.4% cells death occurred in AzaC pre treatment group. After 48h MCF7 cells treated with Dox showed 19.0% cell death while AzaC sensitized cells showed 50.0% cells death when exposed to 500 nM of Dox for 48h. Western blot analysis showed the upregulations in the expression of bax, caspase-3, caspase-9 and p53 in AzaC-sensitized MCF7 cells treated with Dox as compared to those treated with only Dox. There was no clear indication for pro-apoptosis genes in the cells treated with individual drugs. These results showed that pretreatment with the epigenetic modulator significantly increased the sensitivity of MCF7 cells to Dox. Therefore it is concluded that demethylation event might enhance the activity of DNA intercalating agents to induce DNA damage in breast cancer cells.
