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目的:探讨羟苯基维胺脂(4-HPR)联合顺铂(DDP)对卵巢癌SKOV3细胞形态学、增殖、凋亡和细胞周期的影响,及其与血管内皮生长因子(VEGF)、尿激酶型纤溶酶原激活物(u-PA)表达变化的关系。方法:观察不同浓度4-HPR对SKOV3细胞形态学变化;MTT法检测4-HPR、DDP及联合对SKOV3细胞增殖的影响;流式细胞仪检测4-HPR、DDP对SKOV3细胞凋亡和细胞周期的影响;RT-PCR法检测4-HPR、DDP对SKOV3细胞VEGF、u-PAmRNA表达的影响。结果:1μmol/L的DDP对SKOV3细胞增殖抑制作用较弱,≥5μmol/LDDP可明显抑制SKOV3细胞增殖,P<0.05。1μmol/L的4-HPR对SKOV3细胞生长抑制作用不明显,≥2.5μmol/L时,4-HPR对SKOV3细胞生长抑制作用明显增强,P<0.05。5μmol/L的DDP联合4-HPR(1、5和10μmol/L)能显著抑制SKOV3细胞的增殖,两者联合对SKOV3细胞的抑制作用较DDP单独用药明显增强,P<0.05。不同浓度4-HPR和DDP作用SKOV3细胞48h均可诱导细胞凋亡并将细胞阻滞于G2～M期和S期,在两者联合时上述作用更加明显,P<0.05。不同浓度4-HPR和DDP作用SKOV3细胞48h均可抑制细胞VEGF、u-PAmRNA的表达,P<0.01。结论:4-HPR联合DDP能抑制卵巢癌SKOV3细胞增殖,诱导细胞凋亡,阻滞细胞周期,其机制可能与抑制VEGF、u-PA表达有关。
OBJECTIVE: To investigate the effects of 4-HPR combined with cisplatin (DDP) on morphological, proliferation, apoptosis and cell cycle of ovarian cancer cell line SKOV3 and its relationship with vascular endothelial growth factor (VEGF), urine Relationship between the expression of kinases and plasminogen activator (u-PA). Methods: The morphological changes of SKOV3 cells were observed by different concentrations of 4-HPR. The effects of 4-HPR, DDP and combination on the proliferation of SKOV3 cells were detected by MTT assay. The apoptosis and cell cycle of SKOV3 cells were detected by flow cytometry The effects of 4-HPR and DDP on the expression of VEGF and u-PA mRNA in SKOV3 cells were detected by RT-PCR. Results: 1μmol / L DDP had a weak inhibitory effect on SKOV3 cells proliferation, and ≥5μmol / LDDP could significantly inhibit the proliferation of SKOV3 cells. P <0.05.1μmol / L 4-HPR had no obvious inhibitory effect on SKOV3 cells, / L, the inhibitory effect of 4-HPR on SKOV3 cells was significantly enhanced. P <0.05.5μmol / L DDP combined with 4-HPR (1,5 and 10μmol / L) could significantly inhibit the proliferation of SKOV3 cells, The inhibition of SKOV3 cells was significantly higher than that of DDP alone, P <0.05. The apoptosis of SKOV3 cells induced by different concentrations of 4-HPR and DDP for 48h could induce cell apoptosis and arrest the cells in G2-M phase and S phase. The combination of these two effects was more obvious (P <0.05). The SKOV3 cells treated with different concentrations of 4-HPR and DDP for 48h inhibited the expression of VEGF and u-PA mRNA (P <0.01). Conclusion: 4-HPR combined with DDP can inhibit ovarian cancer SKOV3 cell proliferation, induce apoptosis and arrest cell cycle, which may be related to the inhibition of VEGF and u-PA expression.