Abstract
ObjectiveThis study was designed to investigate the effect of combination of ursolic acid (UA) with cisplatin (DDP) on cervical cancer cell proliferation and apoptosis.MethodsThe mRNA and protein expressions of nuclear factor-kappa B (NF-κB) p65 in cervical cancer cells were examined using RT-PCR and western blot. MTT and colony formation assays were performed to examine the DDP toxicity and the proliferation ability of cervical cancer cells. Cell morphology was observed by means of Hoechst33258 and transmission electron microscopy (TEM). The apoptosis rate and cell cycle were assessed through flow cytometry assay. Western blot was used to detect the expression of apoptosis-related molecules.ResultsThe mRNA and protein expressions of NF-κB p65 in cervical cancer cells were significantly higher than that in cervical epithelial cells. The combined treatment of UA and DDP inhibited cervical cancer cell growth and promoted apoptosis more effectively than DDP treatment or UA treatment alone (P < 0.05). Compared with the DDP group and UA group, the expressions of Bcl-2 and NF-κB p65 in DDP +UA group were decreased, while the expressions of Bax, Caspase-3 and PARP cleavage were observably increased. The expression of nuclear NF-κB p65 significantly reduced in UA group and DDP +UA group. si-p65 group displayed a decrease of cell proliferation ability and led to a significant reduction in the number of SiHa cell colony formation.ConclusionThe combination of UA with DDP could more effectively inhibit SiHa cells proliferation and facilitate cell apoptosis through suppressing NF-κB p65.
Highlights
Cervical cancer is considered one of the most common female diseases and a major cause of cancer-related death in female populations [1]
NF-κB p65 expression was up-regulated in cervical cancer cells
The mRNA expression level of NF-κB p65 was significantly increased in cervical cancer cell lines HeLa, SiHa, C-33A and ME-180 when compared with human cervical epithelial cells H8(Figure 1A, all P < 0.01)
Summary
Cervical cancer is considered one of the most common female diseases and a major cause of cancer-related death in female populations [1]. Current therapeutic approaches of the cervical cancer include surgery, chemotherapy and radiotherapy which may be used individually or in combination with other approaches [3, 4]. Both surgical removal and radiotherapy can incur long-term complications or sequela, which may exert negative influence on the prognosis of cervical cancer patients [5]. UA possesses anti-oxidation, antimicrobial, anti-inflammation and anti-tumor properties [7, 8]. Current research has indicated that UA might have an inhibitive function on tumorigenesis and tumor growth [9, 10]. The anti-cancer function of UA has been widely studied, the explicit anti-cancer mechanism of UA remains unknown
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