白藜芦醇通过抑制膀胱癌细胞的糖代谢增强顺铂的抗肿瘤活性

Resveratrol Promotes Cisplatin-induced Cell Death by Inhibiting the Glucose Metabolism in Bladder Cancer

关键词:  白藜芦醇  PKM2  糖代谢  T24  顺铂

Key words:  resveratrol  PKM2  glucose metabolism  T24  cisplatin

摘要:

目的 研究白藜芦醇增强顺铂对膀胱癌细胞的杀伤活性及机制。方法 MTT法和流式细胞术分别检测顺铂单独治疗及联合白藜芦醇治疗对膀胱癌细胞系T24的杀伤活性和凋亡诱导效应。将T24细胞用白藜芦醇和顺铂处理后，检测T24细胞对葡萄糖的摄取能力和乳酸及ATP的生成能力。将T24细胞用白藜芦醇和顺铂处理后，用Western blot方法检测T24细胞PKM2的表达水平。构建PKM2真核表达载体，检测PKM2表达载体对白藜芦醇联合顺铂杀伤T24细胞疗效的影响。结果 白藜芦醇单独治疗在体外对T24细胞的杀伤活性较低，但能显著增强顺铂对T24细胞的杀伤活性。白藜芦醇能显著减弱T24细胞对葡萄糖的摄取和乳酸及ATP的生成并下调T24细胞的PKM2表达水平。转染PKM2表达载体后，白藜芦醇对顺铂的协同抗肿瘤作用受到抑制。结论 白藜芦醇通过下调PKM2的表达抑制肿瘤细胞的糖代谢增强顺铂对膀胱癌细胞的杀伤活性。

Abstract:

OBJECTIVE To investigate the role and mechanism of resveratrol in cisplatin-induced cell death in bladder cancer. METHODS MTT assay as well as flow cytometry was performed to detect the cell death and apoptosis respectively in bladder cancer cell line T24 treated with resveratrol and cisplatin. The uptake of glucose and the production of lactate and ATP were evaluated after the T24 cells were treated with resveratrol and cisplatin. Western blot analysis was performed to detect the expression of PKM2 in T24 cells treated with resveratrol and cisplatin. PKM2 eukaryotic expression vector was conducted to investigate its role in combination treatment with resveratrol and cisplatin in T24. RESULTS Although resveratrol exhibited low anti-tumor effect on T24 cells, it significantly enhanced the cell death induced by cisplatin. Resveratrol significantly impaired the glucose uptake and the production of lactate and ATP in T24 cells. Furthermore, the expression of PKM2 was down-regulated due to the resveratrol treatment. Finally, we found the transfection of PKM2 eukaryotic expression vector abolished the synergistic effect of resveratrol on cisplatin-induced cell death in T24 cells. CONCLUSION Resveratrol promotes cisplatin-induced cell death by inhibiting the glucose metabolism via PKM2 pathway in bladder cancer.