| 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].Chinese Journal of Radiological Medicine and Protection,2025,45(10):949-957 |
| Impacts of PIM2/PFKFB3 signaling pathway-mediated enhancement of glycolysis in pancreatic cancer cells on the anticancer capacity of radiotherapy |
| Received:October 02, 2024 |
| DOI：10.3760/cma.j.cn112271-20241002-00393 |
| KeyWords:131I-NaI Pancreatic cancer Glycolysis 18F-fluorodeoxyglucose(18F-FDG) Proviral integration moloney murineleukemia virus 2(PIM2) |
| FundProject: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) |
| Author Name | Affiliation | E-mail | | Luan Yufen | Department of Nuclear Medicine, Changzhou No. 2 People's Hospital, Changzhou 213000, China | | | Luo Judong | Department of Radiotherapy, Changzhou No. 2 People's Hospital, Changzhou 213000, China | | | Wan Renming | Department of Laboratory, Changzhou No. 2 People's Hospital, Changzhou 213000, China | | | Li Guangyu | Department of Laboratory, Changzhou No. 2 People's Hospital, Changzhou 213000, China | | | Fan Guanglei | Department of Nuclear Medicine, Changzhou No. 2 People's Hospital, Changzhou 213000, China | luckysweet1578@163.com |
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| Abstract:: |
| 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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