| 刘江伟,王 璇,李 鹏,袁 芳,张玉彪,郑树涛,董 翔.二甲双胍增强胰腺癌放疗敏感性的体外及体内实验研究[J].,2017,17(13):2418-2421 |
| 二甲双胍增强胰腺癌放疗敏感性的体外及体内实验研究 |
| Metformin Sensitizes Pancreatic Cells to Radiation in Vitro and in Vivo |
| 投稿时间：2016-11-20 修订日期：2016-12-16 |
| DOI：10.13241/j.cnki.pmb.2017.13.005 |
| 中文关键词: 胰腺癌 二甲双胍 放射敏感性 移植瘤 |
| 英文关键词: Pancreatic cancer Metformin Radiosensitive Xenograft |
| 基金项目:新疆自治区自然科学基金项目(2013211A073) |
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| 中文摘要: |
| 摘要 目的：探讨二甲双胍对胰腺癌细胞和胰腺癌裸鼠移植瘤放疗敏感性的影响。方法：体外培养人胰腺癌BxPC-3和AsPC-1细胞，分为二甲双胍处理组和未处理组，处理组给予10 mmol/L二甲双胍作用48小时后分别给予0、1、2、4、6、8Gy射线对两种细胞进行照射，运用克隆形成实验，Giemsa染色后计算克隆形成率及SF2，并拟合细胞存活曲线。应用裸鼠皮下注射胰腺癌细胞，建立两种细胞的裸鼠移植瘤模型，裸鼠肿瘤体积达到100 mm3时，作为0天，并开始分组，每种移植瘤使用24只裸鼠随机分为4组：生理盐水对照组、单纯二甲双胍治疗组、单纯照射组、二甲双胍+照射组，二甲双胍处理组每天给予250 mg/kg(50 μL/每只)腹腔注射，对照组仅给予等量生理盐水注射(50 μL /每只)。每4天用游标卡尺测量移植瘤的长径和宽径，并绘制生长曲线。当对照组体积达到200 mm3时，照射组和联合组，给予一次性照射6Gy 射线，当对照组体积达到1000 mm3时，将裸鼠进行麻醉，剥出皮下移植瘤，进行称量和保存，并计算抑瘤率。结果：两细胞系经过二甲双胍处理后，经2、4、6、8Gy照射后存活分数明显低于未处理组(P<0.01)，随着照射剂量的增大，克隆形成数量明显减少，两个细胞系经二甲双胍处理后进行照射，其SF2、D0, N值均较未处理组明显减少(P<0.01)，表明经二甲双胍处理后，BxPC-3细胞和AsPC-1细胞的放射敏感性增强，增敏比分别为1.2368 和1.1179。二甲双胍和放射联合处理组的体积、瘤重均明显小于对照组和单独处理组，BxPC-3和AsPC-1移植瘤的抑瘤率分别为62.14%、61.53%，均明显高于各自单独处理组(P<0.01或P<0.05)。结论：二甲双胍能够增强胰腺癌的放疗敏感性，在临床上具有潜在的应用价值。 |
| 英文摘要: |
| ABSTRACT Objective: To examine the potential of metformin (MET) to enhance pancreatic cancer (PC) responses to ionising radi- ation (IR). Methods: Pancreatic cancer cell line BxPC-3 and AsPC-1 were cultured, then they were divided into 2 groups: the control group and metformin treated group, the metformin treated group were given 10mM metformin 48h before irradiated with X-ray irradia- tion at 0, 1, 2, 4, 6, 8Gy. The clone formation assay were used and Giemsa stained colony formation rate and SF2 were calculated and the fitting cell survival curve were made at the same time. In vivo experiment, the cell suspension of BxPC-3 and AsPC-1 were injected sub- cutaneously into the right anterior armpit of nude mice, to establish a xenograft model. In each cell line, treatment was initiated when the tu- mor volume reached 100 mm3, and the 1st day of treatment in both cases was designated as day 0, the 24 injected mice were randomly di- vided into four groups: NS-treated control, MET-treated alone, ionising radiation (IR) treated alone, MET-treated combination IR(n=6, per group), For injection, metformin was dissolved in sterile saline and was intraperitoneally injected once per day at 250 mg/kg(50 μL/mouse). The control group received vehicle only (50 μL saline). Tumor volume (V) was measured by external caliper every 4 days and the growing curve were made. When the volume were reached 200 mm3, the IR group and the MET-treated combination IR group were given 6Gy X-ray irradiation for once, Mice were sacrificed at the 28th day and the weights of xenografts were measured and the in- habitation rate were calculated. Results: The survival fraction were significantly decreased in the MET treated cell group than the un- treated group in the both cell lines after irradiated with X-ray of 2, 4, 6, 8 Gy. The colony formation were decreased with the increasing of the X-ray. The SF2, D0 and N were decreased in MET treated group compared with the control group(P<0.01), which indicated that the radiosensitivity after the treatment of the MET, and the ER of the BxPC-3 and AsPC-1 cells were 1.2368 and 1.1179, respectively. In the experiment of nude mice, the tumor inhibition were obvious in the IRMET-treated combination IR group than the MET alone, IR alone and control group, and the inhibition rate were 62.14% and 61.53% respectively for the BxPC-3 and AsPC-1 xenograft mode(P<0.01 or P<0.05). Conclusion: Clinically achievable MET doses inhibit pancreatic cancer cell and tumour growth and sensitise them to IR. Our results suggest that MET can be a clinically useful adjunct toradiotherapy in pancreatic cancer. |
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