Zhang Jin, Yuan Baozhu, Zhang Huidan, Li Hongxia
Department of Obstetrics and Gynaecology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
Cell Collection and Research Centre, National Institutes for Food and Drug Control, Beijing 100050, P.R. China.
Oncol Lett. 2019 Jun;17(6):5351-5360. doi: 10.3892/ol.2019.10221. Epub 2019 Apr 5.
The high rate of mortality associated with ovarian cancer (OC) is due in part to the development of resistance to chemotherapy, which allows the resistant tumour cells to invade and metastasise. Clarifying the mechanistic basis for drug resistance may reveal novel avenues for treatment. The present study investigated the mechanism of paclitaxel (PTX) resistance in human epithelial OC by evaluating the expression of stem cell-associated cell surface markers endoglin (CD105), CD44 antigen and vascular cell adhesion molecule 1 (CD106), in association with the malignant potential of the human OC OVCAR3 cell line and its PTX-resistant derivative OC3/TAX300. The expression of CD105, CD44 and CD106 was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and flow cytometry, and cell invasion was evaluated using a Transwell invasion assay. CD105, CD44 and CD106 levels were increased in OC3/TAX300 cells compared with the OVCAR3 cells, as determined by flow cytometry (P<0.01) and RT-qPCR (P<0.05). Additionally, the number of invading cells was increased in the OC3/TAX300 group compared with the OVCAR3 group (54.7±6.65 vs. 31.8±6.55; P<0.01). A western blot analysis of cell surface marker expression in 80 clinical epithelial OC tissue samples, differing in terms of sensitivity to drug treatments, disease stage and degree of differentiation, revealed that high CD105, CD44 or CD106 expression was associated with drug resistance, advanced disease stage, poor differentiation and high rate of recurrence. These data indicated that exposure to high doses of PTX enhanced the stem-like properties of OC cells, which are associated with drug resistance and invasion and lead to poor prognosis due to induced chemoresistance and/or metastasis. Therefore, CD105, CD44 and CD106 may serve as potential stem cell-associated cell surface and prognostic markers, and therapeutic targets, in OC.
卵巢癌（OC）的高死亡率部分归因于对化疗产生耐药性，这使得耐药肿瘤细胞能够侵袭和转移。阐明耐药的机制基础可能会揭示新的治疗途径。本研究通过评估干细胞相关细胞表面标志物内皮糖蛋白（CD105）、CD44抗原和血管细胞黏附分子1（CD106）的表达，结合人OC OVCAR3细胞系及其耐紫杉醇（PTX）衍生物OC3/TAX300的恶性潜能，研究了人上皮性OC中PTX耐药的机制。通过逆转录定量聚合酶链反应（RT-qPCR）和流式细胞术检测CD105、CD44和CD106的表达，并使用Transwell侵袭试验评估细胞侵袭。流式细胞术（P<0.01）和RT-qPCR（P<0.05）检测结果显示，与OVCAR3细胞相比，OC3/TAX300细胞中CD105、CD44和CD106水平升高。此外，与OVCAR3组相比，OC3/TAX300组的侵袭细胞数量增加（54.7±6.65对31.8±6.55；P<0.01）。对80例临床上皮性OC组织样本进行细胞表面标志物表达的蛋白质印迹分析，这些样本在药物治疗敏感性（对药物治疗的敏感性）、疾病分期和分化程度方面存在差异，结果显示CD105、CD44或CD106高表达与耐药、疾病晚期、低分化和高复发率相关。这些数据表明，暴露于高剂量PTX会增强OC细胞的干细胞样特性，这与耐药性和侵袭相关，并由于诱导的化疗耐药性和/或转移导致预后不良。因此，CD105、CD44和CD106可能作为OC中潜在的干细胞相关细胞表面标志物和预后标志物以及治疗靶点。
