RBBP6: a potential biomarker of apoptosis induction in human cervical cancer cell lines.
RBBP6: a potential biomarker of apoptosis induction in human cervical cancer cell lines.
复制标题
DOI：
10.2147/ott.s100964
复制
发表时间：
2016
影响因子：
4
通讯作者：
Motadi LR
中科院分区：
文献类型：
--
作者：
Moela P;Motadi LR
RBBP 6在结肠癌、肺癌和食管癌中的过表达使其成为抗癌治疗的潜在靶点。这一点尤其重要，因为RBBP 6与肿瘤抑制基因p53相关，其失活与超过50%的所有癌症类型有关。然而，RBBP 6在癌症中的表达及其与p53的相互作用尚未被理解，以确定RBBP 6是否是癌症促进剂，因此是否是潜在的生物标志物。在这项研究中，我们操纵RBBP 6的表达水平，然后用喜树碱或γ-氨基丁酸处理宫颈癌细胞，以诱导细胞凋亡或细胞周期阻滞。我们首先用抗RBBP 6单克隆抗体对人宫颈癌组织切片进行染色，以评估患者标本中RBBP 6的表达程度。我们接着沉默RBBP 6的过表达并用抗癌药物治疗，以评估标本对联合治疗的反应。通过共聚焦显微镜和使用膜联蛋白V染色的流式细胞术以及通过检查线粒体和半胱天冬酶-3/7活性来评估凋亡诱导。通过碘化丙啶染色，使用流式细胞术评估细胞周期停滞。RBBP 6在处于发展阶段II或III的宫颈癌组织切片中高度表达。沉默RBBP 6后用γ-氨基丁酸和喜树碱处理似乎使细胞对凋亡诱导而不是细胞周期停滞敏感。RBBP 6的过表达可能促进细胞周期中的S期和细胞增殖。这些结果预测了RBBP 6在癌症进展中的增殖作用，而不是作为致癌基因。此外，通过RBBP 6靶向使细胞对喜树碱诱导的细胞凋亡敏感，提示了阻止宫颈癌进展的有希望的工具。
Overexpression of RBBP6 in cancers of the colon, lung, and esophagus makes it a potential target in anticancer therapy. This is especially important because RBBP6 associates with the tumor suppressor gene p53, the inactivation of which has been linked to over 50% of all cancer types. However, the expression of RBBP6 in cancer and its interaction with p53 are yet to be understood in order to determine whether or not RBBP6 is cancer promoting and therefore a potential biomarker. In this study, we manipulated RBBP6 expression levels followed by treatment with either camptothecin or γ-aminobutyric acid in cervical cancer cells to induce apoptosis or cell cycle arrest. We began by staining human cervical cancer tissue sections with anti-RBBP6 monoclonal antibody to evaluate the extent of expression of RBBP6 in patients’ specimens. We followed on with silencing the overexpression of RBBP6 and treatment with anticancer agents to evaluate how the specimens respond to combinational therapy. Apoptosis induction was evaluated through confocal microscope, and flow cytometry using annexin V staining, and also by checking the mitochondrial and caspase-3/7 activity. Cell cycle arrest was evaluated using flow cytometry through staining with propidium iodide. RBBP6 was highly expressed in cervical cancer tissue sections that were in stage II or III of development. Silencing RBBP6 followed by treatment with γ-aminobutyric acid and camptothecin seems to sensitize cells to apoptosis induction rather than cell cycle arrest. Overexpression of RBBP6 seems to promote S-phase in cell cycle and cell proliferation. These results predict a proliferative role of RBBP6 in cancer progression rather than as a cancer-causing gene. Furthermore, sensitization of cells to camptothecin-induced apoptosis by RBBP6 targeting suggests a promising tool for halting cervical cancer progression.