| Summary: | 碩士 === 國立中山大學 === 生物醫學研究所 === 104 === Breast cancer is a leading cause of death in women worldwide, and chemotherapy is one of the primary strategies for breast cancer treatment. However, the chemoresistance often causes the poor prognosis of breast cancer patients. Phthalate derivatives have been shown to affect the expression of genes, and could take effects on genotoxic sensitivity and the ability of DNA repair in cells. Recent evidence suggested that phthalate exposure may be closely correlated with the chemoresistance of breast cancer cells. However, the underlying mechanism that phthalate causes chemoresistance is largely unclear. In the study, we investigated whether phthalates affect the chemoresistance by reinforcing the ability of DNA repair. Our results showed that phthalate Bis(2-ethylhexyl) phthalate (DEHP) attenuates the camptothecin (CPT)-induced DNA damage in breast cancer cells MCF-7. Moreover, phthalate DEHP pre-treatment significantly inhibits the two hallmarks of double-strand breaks (DSB) of DNA, including γH2AX and the phosphorylation of ATM, which were significantly reduced in CPT-treated MCF-7 cells. Consistently, the results of zebrafish xenograft assay confirmed the protective effect of DEHP on CPT-induced cytotoxicity of breast cancer. Accordingly, our present work suggests that phthalate DEHP may affect the anti-breast cancer effect of CPT through attenuating the induction of DNA damage.
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