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黄精多糖对膀胱癌细胞增殖的抑制作用及其机制研究
王金铸,蔡科科,杨拓,刘立朋
天津市中西医结合医院泌尿外科,南开大学附属南开医院,天津市急腹症器官损伤与中西医修复重点实验室天津 300110
摘要:
目的:探讨中药黄精多糖(PSP)抑制膀胱癌(BC)细胞的增殖及其作用机制。方法:采用不同浓度(0、20、50 μg/mL)的PSP与BC细胞系T24和5637培养24 h,通过CCK-8法、集落形成实验评估PSP对T24和5637细胞增殖的抑制作用;免疫印迹法检测PSP对糖酵解的抑制作用、糖酵解相关蛋白的表达与细胞凋亡的相关性。结果:与对照组(0 μg/mL PSP)相比,实验组(20、50 μg/mL PSP)能显著抑制BC细胞的增殖,在20 μg/mL浓度下两种细胞系的存活率分别降至58%和52%,而在50 μg/mL浓度下两种细胞系的存活率分别降至32%和27%(P <0.001),并显著抑制集落形成(P <0.001);PSP能显著促进BC细胞凋亡,凋亡比例随PSP浓度增加而增加,且B细胞淋巴瘤-2蛋白(Bcl-2)相关X蛋白(Bax)和活化的caspase-3(cleaved caspase-3)显著增加,Bcl-2显著降低(P <0.001)。PSP能显著抑制BC细胞系糖酵解及相关蛋白的表达,己糖激酶2(HK2)和乳酸脱氢酶A(LDHA)的表达水平显著降低,并具有梯度效应(P <0.001);PSP处理显著抑制信号转导与转录激活因子3(STAT3)的磷酸化水平并降低Toll样受体4(TLR4)的表达(P <0.001),提示PSP通过抑制TLR4/STAT3信号通路抑制BC细胞凋亡与增殖。结论:中药提取物PSP对BC细胞的糖酵解和抑制TLR4/STAT3信号通路是促进BC细胞凋亡和抑制其增殖的主要作用机制。
关键词:  膀胱癌  黄精多糖  糖酵解  集落形成  凋亡  TLR4/STAT3
DOI:10.3969/j.issn.1007-6948.2025.04.005
投稿时间:2025-02-12
基金项目:
Inhibitory effect of polygonatum polysaccharide on proliferation of bladder cancer cells
WANG Jin-zhu,CAI Ke-ke,YANG Tuo
Department of Urology, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Nankai University Affiliated Nankai Hospital, Tianjin Key Laboratory of Acute Abdominal Organ Injury and Repair of Traditional Chinese and Western Medicine, Tianjin300110, China
Abstract:
Objective To investigate the inhibitory effects of polygonatum sibiricum polysaccharide (PSP) on the proliferation of bladder cancer (BC) cells and explore the underlying mechanisms. Methods T24 and 5637 bladder cancer cell lines were treated with PSP for 24 hours. Cell viability was assessed by CCK-8 assay, and colony formation assay was used to evaluate cell growth and proliferation. Immunoblotting was employed to analyze apoptosis, and was used to detect the expression of glycolysis-related proteins to explore the inhibitory effect of PSP on glycolysis. Results Compared with the control group, PSP significantly inhibited the proliferation of bladder cancer cells, cell viability decreased to 58% and 52% at 20 μg/mL, and decreased to 32% and 27% at 50 μg/mL (P <0.001), and significantly inhibited colony formation (P <0.001). PSP significantly promoted the apoptosis of bladder cancer cells, and the percentage of apoptosis increased with the increase of PSP concentration, Bax and cleaved caspase-3 were significantly increased, and Bcl-2 was significantly decreased, indicating the promotion of apoptosis (P <0.001). PSP could significantly inhibit the expression of glycolysis and related proteins in bladder cancer cell lines, and the expression levels of HK2 and LDHA were significantly decreased, with gradient effect (P <0.001); PSP treatment significantly inhibited the phosphorylation of STAT3 and decreased the expression of TLR4 (P <0.001), indicating that PSP is a molecular pathway that inhibits the apoptosis and proliferation of bladder cancer by inhibiting TLR4/STAT3 signaling pathway. Conclusion PSP is a potential therapeutic agent for bladder cancer, capable of inhibiting cell proliferation, promoting apoptosis, suppressing glycolysis, and exerting its effects through the TLR4/STAT3 signaling pathway, demonstrating significant potential in the treatment of bladder cancer.
Key words:  Bladder cancer  polygonatum sibiricum polysaccharide  glycolysis  colony formation  apoptosis  TLR4/STAT3

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