Arsenic Trioxide Promotes Paclitaxel Cytotoxicity in Resistant Breast Cancer Cells

Bakhshaiesh, Tayebeh Oghabi; Armat, Marzie; Shanehbandi, Dariush; Sharifi, Simin; Baradaran, Behzad; Hejazi, Mohammad Saeed; Samadi, Nasser

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자료유형: 학술저널

저자정보: Bakhshaiesh, Tayebeh Oghabi (Drug Applied Research Centre) Armat, Marzie (Drug Applied Research Centre) Shanehbandi, Dariush (Immunology Research Center) Sharifi, Simin (Department of Pharmaceutical Biotechnology, Faculty of Pharmacy) Baradaran, Behzad (Immunology Research Center) Hejazi, Mohammad Saeed (Drug Applied Research Centre) Samadi, Nasser (Drug Applied Research Centre)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제13호

발행연도: 2015.1

수록면: 5,191 - 5,197 (7page)

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A partial response or resistance to chemotherapeutic agents is considered as a main obstacle in treatment of patients with cancer, including breast cancer. Refining taxane-based treatment procedures using adjuvant or combination treatment is a novel strategy to increase the efficiency of chemotherapy. PPM1D is a molecule activated by reactive oxygen species. whose expression is reported to modulate the recruitment of DNA repair molecules. In this study we examined the impact of arsenic trioxide on efficacy of paclitaxel-induced apoptosis in paclitaxel-resistant MCF-7 cells. We also investigated the expression of PPM1D and TP53 genes in response to this combination treatment. Resistant cells were developed from the parent MCF-7 cell line by applying increasing concentrations of paclitaxel. MTT assays were applied to determine the rate of cell survival. DAPI staining using fluorescent microscopy was employed to study apoptotic bodies. Real-time RT-PCR analysis was also applied to determine PPM1D mRNA levels. Our results revealed that combination of arsenic trioxide and paclitaxel elevates the efficacy of the latter in induction of apoptosis in MCF-7/PAC resistant cells. Applying arsenic trioxide also caused significant decreases in PPM1D mRNA levels (p<0.05). Our findings suggest that arsenic trioxide increases paclitaxel-induced apoptosis by down regulation of PPM1D expression. PPM1D dependent signaling can be considered as a novel target to improve the efficacy of chemotherapeutic agents in resistant breast cancer cells.

#Combination therapy #arsenic trioxide #resistant breast cancer #taxanes #Wip1

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