Triptolide Regulates Cisplatin Resistance and Angiogenesis in Cervical Cancer
Objective:To explore the mechanism of triptolide in regulating cisplatin(DDP)resistance and angiogenesis in cervical cancer through microRNA-138-5p(miR-138-5p)and chromatin remodeling factor 1(RSF-1).Methods:In vitro experiments were conducted using human cervical cancer cells(HeLa),human embryonic kidney cells(293 T),and human umbilical vein endothelial cells(HUVEC).HeLa/DDP-resistant cell lines were established.HeLa/DDP cells were randomly divided into cisplatin+HeLa/DDP group,triptolide+cisplatin+HeLa/DDP group,triptolide+cisplatin+miR-138-5p inhibitor+HeLa/DDP group,and triptol-ide+cisplatin+miR-138-5p inhibitor+si-RSF-1+HeLa/DDP group.The 293T cells were divided into NC mimic group and miR-138-5p mimic group.HUVECs were categorized into cisplatin+HUVEC group,triptolide+cisplatin+HUVEC group,triptolide+cisplatin+miR-138-5p inhibitor+HUVEC group,and triptolide+cisplatin+miR-138-5p inhibitor+si-RSF-1+HUVEC group.The proliferation rate,migration ability,levels of miR-138-5p and RSF-1 were measured,and the targeting relationship between RSF-1 and miR-138-5p,as well as its effect on tube formation,were verified.Results:Compared to the cisplatin+HeLa/DDP group,the proliferation rate and migration ability of the triptolide+cisplatin+HeLa/DDP group decreased at 24,48,and 72 h(all P＜0.05).In the triptolide+cisplatin+HeLa/DDP group,miR-138-5p levels significantly increased while RSF-1 levels decreased(both P＜0.05)compared to the cisplatin+HeLa/DDP group.In the triptolide+cisplatin+miR-138-5p inhibitor+HeLa/DDP group,miR-138-5p expression levels significantly decreased while RSF-1 levels increased(both P＜0.05)compared to the triptol-ide+cisplatin+HeLa/DDP group.Compared with the triptolide+cisplatin+miR-138-5p inhibitor+HeLa/DDP group,the triptol-ide+cisplatin+miR-138-5p inhibitor+si-RSF-1+HeLa/DDP group showed no significant difference in miR-138-5p levels(P＞0.05),but RSF-1 levels significantly decreased(P＜0.05).Co-transfection of RSF-1-WT with miR-138-5p mimic resulted in re-duced luciferase activity compared to the NC mimic group.The number of tubular structures formed was significantly lower in the triptolide+cisplatin+HUVEC group than in the cisplatin+HUVEC group,and also decreased in the triptolide+cisplatin+miR-138-5p inhibitor+HUVEC group than in the triptolide+cisplatin+HUVEC group.Moreover,the number of tubular structures formed was significantly lower in the triptolide+cisplatin+miR-138-5p inhibitor+si-RSF-1+HUVEC group than in the triptolide+cisplatin+miR-138-5p inhibitor+HUVEC group(all P＜0.05).Conclusion:Triptolide can improve DDP resistance and angiogenesis in cervical cancer cells,potentially through the miR-138-5p/RSF-1 pathway.
TriptolideCervical cancerMicroRNA-138-5pRemodeling and spacer factor 1CisplatinDrug resistanceAngio-genesisCell proliferation
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