School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu, P.R. China.
Oncol Rep. 2013 Sep;30(3):1113-8. doi: 10.3892/or.2013.2567. Epub 2013 Jun 26.
Epithelial ovarian cancer is a major cause of mortality among women with gynecological malignancies. Paclitaxel is commonly used for chemotherapy of ovarian cancer, yet its efficacy is limited by chemoresistance. Generally, drug resistance is associated with acquisition of the epithelial-mesenchymal transition (EMT) in cancer. The aim of the present study was to determine whether the EMT is involved in acquired resistance to paclitaxel in A2780 human ovarian cancer cells. Using the paclitaxel-resistant A2780/PTX cell line, we examined the cellular morphology, molecular changes, migration and proliferation consistent with the EMT. Furthermore, we found that inhibition of phosphatidylinositol 3-kinase (PI3K) activity reduced the proliferation and migration and restored their sensitivity to paclitaxel. Our study provides new insights into EMT-like phenotypic changes that are linked to paclitaxel resistance in A2780 cells. We believe that inhibition of the PI3K signaling pathway could provide a novel therapeutic approach to overcome chemoresistance and prevent metastasis during paclitaxel chemotherapy.
上皮性卵巢癌是妇科恶性肿瘤患者死亡的主要原因。紫杉醇通常用于卵巢癌的化疗，但由于化疗耐药性，其疗效受到限制。通常，药物耐药性与癌症中上皮-间充质转化（EMT）的获得有关。本研究旨在确定 EMT 是否参与了人卵巢癌细胞 A2780 对紫杉醇的获得性耐药。使用紫杉醇耐药的 A2780/PTX 细胞系，我们检查了与 EMT 一致的细胞形态、分子变化、迁移和增殖。此外，我们发现抑制磷脂酰肌醇 3-激酶（PI3K）活性可降低增殖和迁移，并恢复其对紫杉醇的敏感性。我们的研究为 EMT 样表型变化与 A2780 细胞紫杉醇耐药性之间的关系提供了新的见解。我们认为，抑制 PI3K 信号通路可能为克服化疗耐药性和预防紫杉醇化疗期间转移提供一种新的治疗方法。
