斯钙素2在卵巢癌发生和进展中的作用及机理研究

来源 :第三届全国暨国际超声分子影像及生物效应和治疗学术会议 | 被引量 : 0次 | 上传用户:onlibao
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  背景 分泌型蛋白斯钙素(Stanniocalcin,STC)在鱼类中参与调节钙磷平衡.人类STC包含STC1和STC2两个成员,均和多种肿瘤有关.RAS转化的卵巢癌细胞中STC1水平升高,并促进肿瘤的发生,但STC2在卵巢癌中的作用还不清楚.目的 研究STC2在卵巢癌发生中的作用及机制,为卵巢癌的诊断及治疗提供思路.方法 首先在卵巢癌细胞系SKOV3中转染HA-tag标记的STC2cDNA,以证明分泌型蛋白STC2可以作用于自身细胞;然后在一系列卵巢癌细胞系中用STC2shRNA或cDNA沉默或过表达STC2,以系统研究STC2对卵巢癌细胞增殖、平板克隆、周期进程、对顺铂和紫杉醇的敏感性及细胞迁移和侵袭能力的影响;并构建动物模型,以观察STC2在体内的作用.结果 STC2可以分泌至细胞外,再从胞外结合到细胞膜上.在Hey、Hey A8、OVCA420、OVCA429细胞中,干扰STC2的表达抑制细胞增殖和平板克隆形成、促进G1-S周期阻滞、促进细胞对顺铂和紫杉醇的敏感性,促进细胞迁移和侵袭;相反,在A2780、SKOV3、SKOV3ip1细胞中,过表达STC2促进细胞增殖和平板克隆形成、促进G1-S周期过渡、抑制顺铂和紫杉醇引起的凋亡,抑制细胞迁移和侵袭.低表达STC2的细胞中细胞周期相关蛋白CDK2、CDK4、CDK6表达较对照组低,而促凋亡蛋白Bax、Bid和cytoC表达较高;过表达STC2的细胞中以上蛋白变化趋势相反.在裸鼠皮下移植瘤实验中,干扰Hey细胞中的STC2抑制肿瘤生长,过表达SKOV3ip1细胞中的STC2促进肿瘤生长;在裸鼠腹腔种植转移模型中,低表达STC2促进腹腔种植转移,而过表达STC2抑制腹腔转移灶的形成.结论 STC2促进卵巢癌细胞增殖和耐药并促进肿瘤生长,但抑制细胞迁移侵袭并抑制腹腔种植转移.
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