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作 者:李伟[1] 李双[1] 贾瑶[1] 栗妍[1] 李莉[1] 汪辉[1] 马丁[1]
机构地区:[1]华中科技大学同济医学院附属同济医院妇产科,湖北武汉430030
出 处:《中国妇幼保健》2014年第25期4159-4161,共3页Maternal and Child Health Care of China
基 金:国家自然科学基金〔81001152〕
摘 要:目的:探讨顺铂诱导宫颈癌细胞衰老过程中葡萄糖调节蛋白78(glucose regulated protein,GRP78)的作用及相关机制。方法:用亚凋亡剂量顺铂诱导宫颈癌细胞衰老;β-半乳糖苷酶染色检测细胞衰老情况;GRP78诱导剂A23187诱导Hela细胞高表达GRP78;siRNA反义抑制GRP78表达;Western blot检测相关蛋白表达情况。结果:亚凋亡剂量顺铂诱导绝大多数宫颈癌细胞发生衰老;A23187上调GRP78表达后顺铂诱导Hela细胞衰老率降低,GRP78表达被反义抑制后顺铂可重新诱导Hela细胞衰老;P53表达被抑制及Cdc2表达增多与GRP78抗衰老作用有关。结论:GRP78蛋白高表达能够抵抗顺铂诱导宫颈癌细胞发生衰老,可作为逆转肿瘤细胞化疗耐药的新靶点。Objective : To explore the role and related mechanisms of glucose - regulated protein 78 ( GRP78 ) in the course of senescence of cervical cancer cells induced by cisplatin. Methods: Sub - apoptosis dose cisplatin was used to induce cervical cancer cells into senescence; cell senescence was detected by β -galactosidase staining; GRP78 inducer A23187 was used to increase GRP78 expression in HeLa cells; GRP78 expression was inhibited by antisense siRNA; related protein expression was detected by Western blot. Results: Thevast majority of cervical cancer cells were induced into senescence with sup -apoptosis dose cisplatin; the senescence rate of HeLa cells treated with cisplatin decreased significantly when GRP78 expression was up -regulated by A23187; when GRP78 expression was inhibited by anti-sense siRNA, HeLa ceils was induced into senescence by cisplatin again; suppression of P53 expression and increase of Cdc2 expression were correlated with anti - senescence effect of GRP78. Conclusion: High expression of GRP78 can resist senescence of cervical cancer cells induced by cisplatin, which can be used as a new target for reversal of tumor cell resistance to chemotherapy.
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