放射诱导的EGFR核转位阻断可增加人宫颈癌细胞放射敏感度
Cancer Research on Prevention and Treatment(2020)
Abstract
目的 探讨抑制EGFR核转位是否会降低人宫颈癌细胞的放射抵抗.方法 Western blot测定pEGFR-T654多肽、pEGFR-T654对照多肽、西妥昔单抗或吉非替尼预处理后X线照射的人宫颈鳞癌CaSki和腺癌HeLa细胞pEGFR-T654和pDNA-PK-T2609的表达;克隆形成法测定存活分数(SF2),单击多靶模型拟合剂量-存活曲线,计算放射增敏比(SER).结果 4 Gy照射后,CaSki和HeLa细胞核EGFR表达呈时间依赖性增加;与对照多肽比较,pEGFR-T654多肽显著降低了CaSki和HeLa细胞核内pEGFR-T654、DNA-PK和pDNA-PK-T2609的表达;与单独放射比较,西妥昔单抗联合放射明显降低了CaSki细胞核EGFR、pEGFR-T654和pDNA-PK-T2609的表达以及克隆形成率和存活分数(SF2=31.030),增加CaSki细胞的放射敏感度(SER=2.34).结论 放射诱导pEGFR-T654核转位介导pDNA-PK-T2609的活化,西妥昔单抗抑制pEGFR-T654核转运,降低了DNA-PK介导的宫颈鳞癌放射抵抗.
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Key words
cervical cancer,egfr,dna-pk,radiation therapy
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