Xiaoran Liu,Hongsheng Yu. Low dose radiation enhances susceptibility to cisplatin in resistant ovarian cancer cells via downregulation of ERCC1 and Bcl-2. Oncol Transl Med, 2016, 2: 84-89. |
Low dose radiation enhances susceptibility to cisplatin in resistant ovarian cancer cells via downregulation of ERCC1 and Bcl-2 |
Received:September 16, 2015 Revised:April 06, 2016 |
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KeyWord:Low-dose radiation; ovarian cancer; resistance; SKOV3/DDP; excision repair cross complementing-group 1 (ERCC1); B-cell lymphoma 2 (Bcl-2) |
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Abstract: |
Objective?Ovarian cancer is one of the leading causes of mortality in patients with malignant gynecological tumors. After surgical intervention for ovarian cancer, cisplatin (DDP)-based chemotherapy is the first-line treatment. However, a major challenge to treating ovarian cancer is the development of chemoresistance. Thus, the first aim of this study was to determine whether low-dose radiation could enhance the susceptibility of resistant ovarian cancer cells to DDP. The second aim was to provide new strategies for treating DDP-resistant ovarian cancer by examining its mechanism.
Methods?A cell counting kit-8 (CCK8) assay was performed to measure cell proliferation. Flow cytometry was utilized to quantify the apoptosis of DDP-resistant ovarian cancer cells (SKOV3/DDP) using Annexin V and propidium iodide staining. Real-time quantitative (qPCR) was used to analyze the messenger RNA (mRNA) expression levels of excision repair cross complementing-group 1 (ERCC1) and B-cell lymphoma 2 (Bcl-2) in SKOV3/DDP.
Results?The IC50 values of the control, conventional-dose, and low-dose groups were 9.367 ± 0.16, 9.289 ± 0.16, and 3.847 ± 0.15, respectively (P < 0.05 vs control group and conventional-dose group). Compared with the control and conventional-dose groups, low-dose radiation resulted in significantly more apoptosis, as detected by flow cytometry (P < 0.05). The relative mRNA expression of ERCC1 and Bcl-2 in the low-dose group was significantly lower than that in the control group and conventional-dose group (P < 0.05).
Conclusion?Low-dose radiation enhanced the sensitivity of resistant ovarian cancer cells to DDP, possibly by decreasing the DNA repair capacity of tumor cells and promoting apoptosis.
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