| 栾玉芬,罗居东,万仁明,等.PIM2/PFKFB3信号通路介导的胰腺癌细胞糖酵解增强对放射性治疗的抗癌能力影响[J].中华放射医学与防护杂志,2025,45(10):949-957.Luan Yufen,Luo Judong,Wan Renming,et al.Impacts of PIM2/PFKFB3 signaling pathway-mediated enhancement of glycolysis in pancreatic cancer cells on the anticancer capacity of radiotherapy[J].Chin J Radiol Med Prot,2025,45(10):949-957 |
| PIM2/PFKFB3信号通路介导的胰腺癌细胞糖酵解增强对放射性治疗的抗癌能力影响 |
| Impacts of PIM2/PFKFB3 signaling pathway-mediated enhancement of glycolysis in pancreatic cancer cells on the anticancer capacity of radiotherapy |
| 投稿时间：2024-10-02 |
| DOI：10.3760/cma.j.cn112271-20241002-00393 |
| 中文关键词: 131I-NaI 胰腺癌 糖酵解 氟18-氟代脱氧葡萄糖(18F-FDG) 莫罗尼鼠白血病病毒前病毒整合基因2(PIM2) |
| 英文关键词:131I-NaI Pancreatic cancer Glycolysis 18F-fluorodeoxyglucose(18F-FDG) Proviral integration moloney murineleukemia virus 2(PIM2) |
| 基金项目:江苏省自然科学基金(BK20191157)；常州市卫健委重大项目(ZD202116)；常州市高层次卫生人才培养工程(2022CZBJ071) |
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| 中文摘要: |
| 目的 探讨131I-NaI放射性治疗对诱导莫罗尼鼠白血病病毒前病毒整合基因2(PIM2)和磷酸化果糖-2, 6-二磷酸酶3(PFKFB3)促进胰腺癌细胞的糖酵解和氟18-氟代脱氧葡萄糖(18F-FDG)摄取的影响。方法 细胞实验中，将人胰腺癌细胞1(PANC-1)随机分为对照组、HJ-PI01组、131I-NaI组和HJ-PI01+131I-NaI组4个处理组。通过葡萄糖摄取、乳酸生成的测量和细胞外酸化速率(ECAR)的测量，检测PANC-1细胞的有氧糖酵解能力。动物实验中，体内实验将100 μl(1 × 107个细胞)的细胞悬浮液皮下注射12只nu/nu雌性裸鼠的左下肢，当肿瘤体积达到约60 mm3时，将小鼠按随机数表法分为4组：对照组、HJ-PI01组、131I-NaI组和HJ-PI01+131I-NaI组，每组3只。所有小鼠处理14 d后，进行18F-FDG PET/CT成像，计算移植瘤的最大标准化摄取值(SUVmax)。PET/CT成像检测后收获肿瘤组织采用免疫组织化学法分析PIM2、PFKFB3、Ki-67的表达。结果 在细胞实验中，与对照组相比，HJ-PI01组PANC-1细胞中葡萄糖摄取、乳酸产生、PFKFB3蛋白表达和ECAR均显著减少(t=4.59~13.98，P＜0.05)，131I-NaI组PANC-1细胞中葡萄糖摄取、乳酸产生、PFKFB3蛋白表达和ECAR均显著增加(t=3.36~13.97，P＜0.05)。与131I-NaI组相比，HJ-PI01+131I-NaI组PANC-1细胞中葡萄糖摄取、乳酸产生、PFKFB3蛋白表达和ECAR均显著减少(t=5.14~20.87，P＜0.05)。在动物实验中，与对照组相比，3组肿瘤中18F-FDG摄取的SUVmax显著降低(t=16.48、22.49、32.64，P < 0.001)，并且HJ-PI01+131I-NaI组肿瘤SUVmax显著低于131I-NaI组(t=10.16，P < 0.001)。免疫组织化学分析显示，与131I-NaI组相比，HJ-PI01+131I-NaI组肿瘤组织中Ki-67表达、PIM2/PFKFB3信号通路表达均显著降低(t=3.27、10.73、14.85，P < 0.05)。结论 抑制PIM2/PFKFB3信号通路介导的PANC-1细胞糖酵解增强可以显著提高131I-NaI在胰腺癌中的抗癌能力，为胰腺癌的放射性治疗提供了一种新的策略。 |
| 英文摘要: |
| Objective To explore the impacts of 131I-NaI radiotherapy on the promotion of glycolysis and 18F-fluorodeoxyglucose (18F-FDG) uptake in pancreatic cancer cells via the induction of proviral integration moloney murineleukemia virus 2 (PIM2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3). Methods In the cell experiments, human pancreatic carcinoma cells-1 (PANC-1) were randomly divided into four groups: a control group, an HJ-PI01 group, a 131I-NaI group, and an HJ-PI01 + 131I-NaI group. Their aerobic glycolysis capacity was assessed by measuring glucose uptake, lactate production, and extracellular acidification rate (ECAR). In vivo animal experiments, 12 nu/nu female nude mice were given 100 μl (1 × 107 cells) of cell suspension through subcutaneous injection into the left lower limbs. When the tumor volume reached approximately 60 mm3, these mice were divided into four groups (a control group, a HJ-PI01 group, a 131I-NaI group, and an HJ-PI01+131I-NaI group) using a random number table, with three mice in each group. After 14 days of treatment, 18F-FDG PET/CT imaging was performed to calculate the maximum standardized uptake value (SUVmax) of the xenografts. Following PET/CT imaging, the tumor tissues were harvested and analyzed for PIM2, PFKFB3, and Ki-67 expressions using immunohistochemistry. Results In cell experiments, compared to the control group, the HJ-PI01 group exhibited significant reduction in glucose uptake, lactate production, PFKFB3 protein expression, and ECAR in PANC-1 cells (t = 4.59-13.98, P < 0.05). In contrast, the 131I-NaI group showed significant increases in these parameters (t = 3.36-13.97, P < 0.05). Compared to the 131I-NaI group, the HJ-PI01+131I-NaI group showed significant reduction in glucose uptake, lactate production, PFKFB3 protein expression, and ECAR (t = 5.14-20.87, P < 0.05). In the animal experiments, compared to the control group, the three groups displayed significant decrease in SUVmax of 18F-FDG uptake in tumors (t = 16.48, 22.49, 32.64, P < 0.001). Moreover, the HJ-PI01 + 131I-NaI group exhibite significantly lower SUVmax than the 131I-NaI group (t = 10.16, P < 0.001). Immunohistochemical analysis revealed that the HJ-PI01+131I-NaI group, compared to the 131I-NaI group, showed significantly lower Ki-67 expression and the PIM2/PFKFB3 signaling pathway in tumor tissues (t = 3.27, 10.73, 14.85, P < 0.05). Conclusions Glycolysis enhancement of PANC-1 cells, mediated by the PIM2/PFKFB3 signaling pathway inhibition, can significantly improve the anticancer capacity of 131I-NaI, providing a novel strategy for radiotherapy in pancreatic cancer. |
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