Department of Abdominal Radiation Oncology Ward 2, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Department of Oncology, Dongying People's Hospital, Dongying, Shandong, China.
Bull Exp Biol Med. 2022 Aug;173(4):448-453. doi: 10.1007/s10517-022-05585-1. Epub 2022 Sep 5.
We studied the effect of cytostatic rapamycin on the antitumor activity of 5-fluorouracil (5-FU). To this end, HT-29 cells were treated with 5-FU, or rapamycin, or their combination. The proliferation and apoptosis of treated cells were evaluated using Cell Counting Kit-8 kit and flow cytometry, respectively. The autophagy was evaluated by transmission electron microscopy and Western blotting by the expression of p62, LC3I, and LC3II proteins. 5-FU inhibited proliferation and promoted apoptosis of HT-29 cells, and the combination of 5-FU with rapamycin potentiated both effects. Rapamycin promoted accumulation of autophagosome/autolysosome and enhanced the level of LC3II/LC3I. Thus, rapamycin enhances the antitumor activity of 5-FU by stimulating autophagy and increasing LC3II/LC3I. The results confirm a potential therapeutic strategy for the clinical application of 5-FU.
我们研究了细胞抑制剂雷帕霉素对氟尿嘧啶（5-FU）抗肿瘤活性的影响。为此，用 5-FU、雷帕霉素或两者联合处理 HT-29 细胞。分别用细胞计数试剂盒-8 试剂盒和流式细胞术评估处理细胞的增殖和凋亡。通过透射电子显微镜和 Western blot 法检测 p62、LC3I 和 LC3II 蛋白的表达来评估自噬。5-FU 抑制 HT-29 细胞的增殖并促进其凋亡，5-FU 与雷帕霉素联合使用增强了这两种作用。雷帕霉素促进自噬体/自溶酶体的积累，并增强 LC3II/LC3I 的水平。因此，雷帕霉素通过刺激自噬和增加 LC3II/LC3I 增强了 5-FU 的抗肿瘤活性。这些结果证实了 5-FU 临床应用的一种潜在治疗策略。
