São Paulo State University (Unesp), Institute of Biosciences, Humanities and Exact Sciences (Ibilce), Campus São José do Rio Preto, SP, Brazil.
Universidade Federal de São Paulo - UNIFESP, Post-Graduation in Structural and Functional Biology, SP, Brazil; Faceres School of Medicine, São José do Rio Preto, SP, Brazil.
Biomed Pharmacother. 2020 Sep;129:110331. doi: 10.1016/j.biopha.2020.110331. Epub 2020 Jul 1.
Cisplatin (Cis) is a choice chemotherapy approach to cervical cancer by inducing DNA adducts and subsequent apoptosis. We have investigated the effects of Cis on Annexin A1 (ANXA1) and inhibitor of DNA binding 1 (ID1) proteins expression to elucidate further mechanisms of Cis actions. Human cervical tissue samples from twenty-four patients, with Cervical Intraepithelial Neoplasia (CIN, stage I, II and III), were evaluated to quantified ANXA1 and ID1 expressions. In vitro, human epidermoid carcinoma of the cervix (SiHa cell line) were treated with Annexin A1 peptide (ANXA1), Cis or Cis + ANXA1 to evaluate cell proliferation and migration, cytotoxicity of treatments as well as ANXA1 and ID1 modulations by mRNA and protein expression. Our findings showed expression of ID1 and ANXA1 proteins in tissue samples from Cervical Intraepithelial Neoplasia (CIN) patients, with intense immunological identification of ID1 in the CIN III stage. In SiHa cells, treatments with Cis alone or Cis + ANXA1, increase mRNA expressions of the ANXA1 and reduced the ID1. In agreement, Cis + ANXA1 enhanced ANXA1 protein expression and Cis or Cis + ANXA1 abolished ID1 protein expression. Cell proliferation was reduced after treatment with ANXA1 peptide and more significant after Cis or Cis + ANXA1 treatments. These two last treatments reduced cell viability, by inducing late apoptosis, and impaired cell migration. Together, our data highlight endogenous ANXA1 is involved in Cis therapy for cervical cancer.
顺铂(Cis)通过诱导 DNA 加合物和随后的细胞凋亡,是治疗宫颈癌的一种选择化疗方法。我们研究了 Cis 对膜联蛋白 A1(ANXA1)和 DNA 结合抑制因子 1(ID1)蛋白表达的影响,以进一步阐明 Cis 作用的机制。我们评估了来自 24 名患者的人宫颈组织样本,这些患者患有宫颈上皮内瘤变(CIN,I、II 和 III 期),以定量检测 ANXA1 和 ID1 的表达。在体外,用人宫颈表皮癌细胞系(SiHa 细胞系)用膜联蛋白 A1 肽(ANXA1)、Cis 或 Cis+ANXA1 处理,以评估细胞增殖和迁移、治疗的细胞毒性以及通过 mRNA 和蛋白表达对 ANXA1 和 ID1 的调节。我们的研究结果显示,CIN 患者组织样本中 ID1 和 ANXA1 蛋白的表达,CIN III 期 ID1 的免疫识别明显增强。在 SiHa 细胞中,单独使用 Cis 或 Cis+ANXA1 处理会增加 ANXA1 的 mRNA 表达并减少 ID1。同样, Cis+ANXA1 增强了 ANXA1 蛋白的表达,而 Cis 或 Cis+ANXA1 则消除了 ID1 蛋白的表达。在用 ANXA1 肽处理后,细胞增殖减少,而在用 Cis 或 Cis+ANXA1 处理后,细胞增殖减少更为显著。后两种处理通过诱导晚期细胞凋亡降低细胞活力,并损害细胞迁移。总之,我们的数据强调了内源性 ANXA1 参与了 Cis 治疗宫颈癌。