膜联蛋白A4与妇科肿瘤关系的研究进展

Research Progress of the Relationship between Anxa4 and Gynecologic Tumour

膜联蛋白A4(Anxa4)是膜联蛋白超家族中的重要成员之一,介导细胞凋亡、分化,参与肿瘤的增殖、侵袭和转移、血管发生和化疗耐药等。近年多项研究表明Anxa4在不同类型的卵巢癌及子宫内膜癌等肿瘤中差异表达:相对于化疗敏感的卵巢浆液性癌,化疗抗拒(chemoresistant)的卵巢透明细胞癌高表达Anxa4,恶性程度较高的子宫内膜浆液性癌相对于子宫内膜样腺癌则高表达Anxa4,但相对于母系卵巢浆液性腺癌细胞系,铂类抗拒的子细胞系低表达Anxa4,Anxa4高表达与宫颈癌细胞系He La细胞抗拒化疗药物所诱导的凋亡有关。而Anxa4与上述肿瘤化疗敏感性相关的分子机制涉及钙离子信号等通路调节、化疗药物转运等相关的"非基因转录效应",还有与核因子κB(NF-κB)信号通路相关的"基因转录效应"。就Anxa4与妇科肿瘤间的关系进行综述,探寻分子靶向Anxa4治疗肿瘤的研究依据。

Annexin A4（Anxa4） is an important member of the annexin protein superfamily which mediates cellular apoptosis, differentiation and regulates proliferation, invasion, metastasis, angiogenesis and chemoresistance of cancer. Recent studies showed that Anxa4 has changes in expression levels in many cancers such as different types of ovary and endometrial cancer： chemoresistant ovarian clear cell carcinoma compared with chemosensitive serous adenocarcinoma of the ovary and uterine serous carcinoma with aggressive biological behavior compared with uterine endometrioid carcinoma, Anxa4 is overexpressed. But in comparison with the sensitive parental cell line, Anxa4 is less expressed in the cisplatin-resistant ovarian serous adenocarcinoma cell line. Overexpression of Anxa4 induced resistance against apoptotic stimulation by chemotherapeutic drugs. Anxa4 accomplishes its biological functions associated with tumour chemosensitivity through a non-transcriptional mechanism via the regulation of calcium signals pathway and anti-cancer drugs transport, and also exerts its biological process through a transcriptional mechanism via NF-κB related genomic effect. In the article, we review about studies on the relationship between Anxa4 and gynecologic tumour to provide research data about molecular-targeted Anxa4 treatment.