首页|SKP2/AXIN/P53负反馈环路对放疗诱导的宫颈癌细胞凋亡的影响

SKP2/AXIN/P53负反馈环路对放疗诱导的宫颈癌细胞凋亡的影响

Effect of SKP2/AXIN/P53 negative feedback loop on radiotherapy-induced apoptosis of cervical cancer cells

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目的 探究S期激酶相关蛋白2(SKP2)/轴蛋白(AXIN)/P53蛋白(P53)负反馈环路对放疗诱导的宫颈癌细胞凋亡的影响.方法 构建宫颈癌放疗抵抗细胞株ME180-RR模型;检测放疗诱导后的宫颈癌细胞中SKP2、AXIN、P53 mRNA和蛋白水平;检测SKP2与AXIN、P53与SKP2的相互作用;将ME180-RR细胞分为Control组、sh-NC组、sh-SKP2组、pc-NC组、pc-P53组;检测宫颈癌细胞增殖、凋亡以及Ki67、B淋巴细胞瘤-2相关X蛋白(Bax)蛋白表达.结果 宫颈癌放疗抵抗细胞中SKP2 mRNA和蛋白水平比宫颈敏感细胞高,P53、AXIN mRNA和蛋白水平比宫颈敏感细胞降低(P<0.05).与sh-NC组相比,sh-SKP2组EdU阳性率下降、细胞凋亡率升高,P53、AXIN、Bax表达水平升高,SKP2、Ki67表达下调(P<0.05).SKP2与AXIN有相互作用.与pc-NC组相比,pc-P53组EdU阳性率降低、细胞凋亡率上升,Ki67下调表达,SKP2、P53、Bax上调表达(P<0.05).P53与SKP2有靶向作用.结论 放疗后宫颈癌细胞中SKP2的表达增加,SKP2与AXIN、P53形成负反馈环路,抑制SKP2表达能够抑制宫颈癌的放疗抵抗,促进细胞凋亡.
Objective To investigate the effect of the negative feedback loop of S-phase kinase associated protein 2(SKP2)/AXIN/p53 protein(P53)on radiotherapy-induced apoptosis of cervical cancer cells.Methods The model of cervical cancer radiotherapy resistance cell line ME180-RR was constructed.The mRNA and protein levels of SKP2,AXIN,and P53 were detected in cervical cancer cells induced by radiotherapy.The interaction between SKP2 and AXIN,P53 and SKP2 was detected.ME180-RR cells were divided into Control group,sh-NC group,sh-SKP2 group,pc-NC group,and pc-P53 group.The proliferation,apoptosis,and Ki67 and B lymphoblastoma-2-associated X protein(Bax)protein expression of cervical cancer cells were detected.Results The levels of SKP2 mRNA and protein in cervical cancer radiotherapy resistant cells were higher than those in cervical sensitive cells,while the mRNA and protein levels ofP53 and AXIN were lower than those in cervical sensitive cells(P<0.05).Compared with the sh-NC group,the positive rate of EdU was decreased,the apoptosis rate was increased,the expression levels of P53,AXIN,and Bax were increased,while the expression levels of SKP2 and Ki67 were down-regulated in the sh-SKP2 group(P<0.05).SKP2 interacts with AXIN.Compared with the pc-NC group,EdU posi-tive rate was decreased,apoptosis rate was increased,expression of Ki67 was down-regulated,expression of SKP2,P53 and Bax was up-regulated in pc-P53 group(P<0.05).P53 has a targeting effect on SKP2.Conclusion The expression of SKP2 increases in cervical cancer cells after radiotherapy,and SKP2 forms a negative feedback loop with AXIN and P53.Inhibiting SKP2 expression can inhibit the radiotherapy resistance of cervical cancer and promote cell apoptosis.

cervical cancerS-phase kinase associated protein 2radiation therapyapoptosis

王微微、陈肖静、陆云燕

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南通市肿瘤医院(南通大学附属肿瘤医院)妇科,江苏南通 226000

宫颈癌 S期激酶相关蛋白2 放疗 凋亡

2024

中国优生与遗传杂志
中国优生科学协会

中国优生与遗传杂志

CSTPCD
影响因子:0.527
ISSN:1006-9534
年,卷(期):2024.32(11)