双氢青蒿素联合顺铂对膀胱癌细胞增殖的抑制作用

Inhibitory effect of dihydroartemisinin combined with cisplatin on the proliferation of bladder cancer cells

摘要:

目的 初步了解双氢青蒿素（dihydroartemisinin，DHA）联合顺铂（cisplatin，DDP）抑制膀胱癌细胞增殖、侵袭转移的作用。方法 以膀胱癌细胞T24/5637为研究对象，通过CCK-8分别检测2种细胞系对DDP及DHA的半抑制浓度（half maximal inhibitory concentration，IC₅₀）；流式细胞仪检测DHA与DDP单独及联合应用时对2种细胞系周期和凋亡的影响；划痕实验、Transwell实验检测DHA与DDP单独或联合应用时对膀胱癌细胞迁移、侵袭能力的影响。结果 DDP对5637细胞的IC₅₀为17.10 μg/mL，对T24细胞的IC₅₀为15.28 μg/mL；DHA对5637细胞的IC₅₀约为24.08 μg/mL，对T24细胞的IC₅₀约为32.27 μg/mL。DHA/DDP单独用药组阻滞G₀/G₁、S期作用弱于联合用药组（P<0.05），单独用药及联合用药对G₂/M期的抑制作用无统计学意义。DHA联合DDP可使T24、5637细胞凋亡率明显高于DHA/DDP单独应用（P<0.05），DDP诱导细胞凋亡率明显高于DHA（P<0.05）；在24 h时，2种细胞DHA组迁移面积百分比大于DDP组（P<0.05）及DDP+DHA组（P<0.05），DDP组迁移面积百分比大于DDP+DHA组（P<0.05）。24 h后DHA组抑制率明显小于DDP组（P<0.05）及DDP+DHA组（P<0.05），DDP组抑制率明显小于DDP+DHA组（P<0.05）。结论 DDP+DHA可增强DDP抑制膀胱癌细胞增殖，DDP+DHA可使DDP抑制膀胱癌细胞迁移侵袭的作用进一步增强。

Abstract:

Objective To investigate the effects of dihydroartemisinin（DHA） combined with cisplatin（DDP） on inhibiting the proliferation，invasion and metastasis of bladder cancer cells.Methods The bladder cancer cells T24/5637 were used as research subjects，and half maximal inhibitory concentration（IC₅₀） of DDP and DHA were respectively detected by CCK-8. Flow cytometry was used to detect the effects of DHA and DDP alone or in combination on the cycle and apoptosis of the two cell lines. The effects of DHA and DDP alone or in combination on the migration and invasion of bladder cancer cells were detected by scratch test and Transwell test.Results The IC₅₀ of DDP against 5637 cells and T24 cells were 17.10 μg/mL and 15.28 μg/mL，respectively. The IC₅₀ of DHA was 24.08 μg/mL for 5637 cells and 32.27 μg/mL for T24 cells. The blocking effect of DHA/DDP alone on G₀/G₁ phase was weaker than that of the combination group（P<0.05），and there was no statistical significance in the inhibition effect of DHA/DDP alone and in combination on G₂/M phase. The apoptosis rate of T24 and 5637 cells induced by DHA combined with DDP was significantly higher than that of DHA/DDP alone（P<0.05），and the apoptosis rate induced by DDP was significantly higher than that of DHA（P<0.05）. At 24 h，the percentage of migration area in DHA group was larger than that in DDP group（P<0.05） and DDP+DHA group（P<0.05），and the percentage of migration area in DDP group was larger than that in DDP+DHA group（P<0.05）. After 24 h，the inhibitory rate of DHA group was significantly lower than that of DDP group（P<0.05） and DDP+DHA group（P<0.05），and the inhibitory rate of DDP group was significantly lower than that of DDP+DHA group（P<0.05）.Conclusion DDP+DHA could enhance the inhibitory effect of DDP on the proliferation of bladder cancer cells，and DDP+DHA could further enhance the inhibitory effect of DDP on the migration and invasion of bladder cancer cells.