| 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. |
| 低剂量辐射通过下调ERCC1和Bcl-2增强耐药卵巢癌细胞对顺铂的敏感性 |
| 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 |
| DOI：10.1007/s10330-015-0119-3 |
| 中文关键词: 低剂量辐射; 卵巢癌; 耐药; SKOV3/DDP; ERCC1; Bcl-2 |
| 英文关键词: 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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| 中文摘要: |
| 目的：在妇科恶性肿瘤中卵巢癌是导致死亡的主要原因之一。卵巢癌手术治疗后,顺铂为基础的化疗是主要的治疗方法。然而，对抗卵巢癌的主要挑战是耐药性的产生。所以本研究的目的是证实低剂量辐射有增强耐药卵巢癌细胞对于顺铂敏感性的作用，并探究其机制，然后为治疗耐药性卵巢癌提供新的策略。方法：CCK8法检测细胞增殖。流式细胞术（FCM）的方法通过Annexin V-FITC和PI染色来量化顺铂耐药的卵巢癌细胞（SKOV3/ DDP）的凋亡率。实时荧光定量RT-PCR分析SKOV3/ DDP 细胞中ERCC1和Bcl-2的mRNA表达水平。结果：对照组，常规剂量组和低剂量组的IC 50值分别为9.367±0.16,9.289±0.16和3.847±0.15分别（P <0.05，与对照组和常规剂量组比较）。通过流式细胞仪检测，与对照组和常规剂量组相比，低剂量辐射组具有更显著的凋亡率（ p <0.05）。低剂量组ERCC1和Bcl-2的mRNA相对表达量比对照组及常规剂量组显著降低（p<0.05）。结论：低剂量辐射具有增强耐药性卵巢癌细胞对顺铂敏感性的作用，并且低剂量辐射可能是通过降低肿瘤细胞的DNA修复能力和促进细胞凋亡来发挥这一作用的。 |
| 英文摘要: |
| 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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