Department of Oncology, Ya'an People's Hospital, 625000 Ya'an, Sichuan, China.
Discov Med. 2024 Jul;36(186):1464-1476. doi: 10.24976/Discov.Med.202436186.136.
Monotherapy consisting of radiotherapy or chemotherapy has limited efficacy in pancreatic tumors. This study aims to investigate whether the combination of I brachytherapy and gemcitabine (GEM) chemotherapy has a synergistic effect on pancreatic cancer (PC).
, PANC-1 cells in the exponential phase were treated with I radioactive seeds (6 Gy) and GEM (30 nM). Cell proliferation, apoptosis, and mitochondrial membrane potential were measured using the Cell Counting Kit-8 (CCK-8) assay, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and flow cytometry, respectively. , we examined the inhibitory effect of three different treatment regimens on tumor growth in mice when combined with I brachytherapy and GEM. Next, we investigated the effects of the optimal scheme among the three on the tumor microenvironment, tumor tissue morphology, tumor cell apoptosis, systemic inflammatory response, and levels of apoptosis-related proteins in the tumor. Changes in the tumor microenvironment and levels of apoptosis-related proteins were measured by Western blot. The extent of damage to tumor tissue morphology was assessed by Hematoxylin and Eosin (HE) staining. Tumor cell apoptosis was measured by TUNEL staining. Changes in inflammation-related factors were determined by Enzyme-Linked Immunosorbent Assay (ELISA).
The results of cell experiments demonstrated that the combination of I radioactive seeds (6 Gy) and GEM (30 nM) had a stronger inhibitory effect on PANC-1 cells than either alone ( < 0.05). , data showed that the GEM (after 3 d) + I treatment group had the strongest tumor inhibition effect on PC ( < 0.05). Western blot analysis showed that the combined treatment of I brachytherapy and GEM caused changes in the expression of collagen and connexin in the tumor microenvironment, promoted tumor cell apoptosis, upregulated the expression of pro-apoptotic proteins, and helped to restore pancreatic function ( < 0.01).
Our research results suggest that the strategy of I seed implantation surgery in mice after 3 days of GEM treatment has a more pronounced synergistic effect on the treatment of PC.
单纯放疗或化疗的单药疗法在胰腺肿瘤中的疗效有限。本研究旨在探讨近距离放射治疗联合吉西他滨（GEM）化疗对胰腺癌（PC）是否具有协同作用。
采用细胞计数试剂盒-8（CCK-8）检测、末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）染色和流式细胞术分别检测 I 放射性种子（6 Gy）和 GEM（30 nM）处理指数期 PANC-1 细胞后的细胞增殖、细胞凋亡和线粒体膜电位。进一步采用皮下接种 PANC-1 细胞建立裸鼠皮下移植瘤模型，分别于接种后第 3 天和第 7 天行 I 放射性种子植入术，同时给予 GEM 腹腔注射。然后检测三种不同治疗方案联合 I 近距离放射治疗对肿瘤生长的抑制作用。进一步探讨三种方案中最佳方案对肿瘤微环境、肿瘤组织形态、肿瘤细胞凋亡、全身炎症反应和肿瘤组织中凋亡相关蛋白水平的影响。采用 Western blot 检测肿瘤微环境和凋亡相关蛋白水平的变化，苏木精和伊红（HE）染色评估肿瘤组织形态损伤程度，TUNEL 染色检测肿瘤细胞凋亡，酶联免疫吸附试验（ELISA）检测炎症相关因子变化。
细胞实验结果表明，I 放射性种子（6 Gy）联合 GEM（30 nM）对 PANC-1 细胞的抑制作用强于单独使用任何一种药物（ < 0.05）。动物实验结果显示，GEM（3 d 后）+ I 治疗组对 PC 的肿瘤抑制作用最强（ < 0.05）。Western blot 分析显示，I 近距离放射治疗联合 GEM 治疗导致肿瘤微环境中胶原和连接蛋白的表达发生变化，促进肿瘤细胞凋亡，上调促凋亡蛋白表达，有助于恢复胰腺功能（ < 0.01）。
本研究结果提示，GEM 治疗 3 天后行 I 种子植入术的策略对 PC 的治疗具有更显著的协同作用。
