RKIP Inhibition in Cervical Cancer Is Associated with Higher Tumor Aggressive Behavior and Resistance to Cisplatin Therapy
نویسندگان
چکیده
Cervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial lesions and carcinomas, were analyzed for RKIP expression by immunohistochemistry. We found that RKIP expression was significantly decreased during malignant progression, being highly expressed in non-neoplastic tissues (54% of the samples; 73/135), and expressed at low levels in the cervix invasive carcinomas (∼15% (19/124). Following in vitro downregulation of RKIP, we observed a viability and proliferative advantage of RKIP-inhibited cells over time, which was associated with an altered cell cycle distribution and higher colony number in a colony formation assay. An in vitro wound healing assay showed that RKIP abrogation is associated with increased migratory capability. RKIP downregulation was also associated with an increased vascularization of the tumors in vivo using a CAM assay. Furthermore, RKIP inhibition induced cervical cancer cells apoptotic resistance to cisplatin treatment. In conclusion, we described that RKIP protein is significantly depleted during the malignant progression of cervical tumors. Despite the lack of association with patient clinical outcome, we demonstrate, in vitro and in vivo, that loss of RKIP expression can be one of the factors that are behind the aggressiveness, malignant progression and chemotherapy resistance of cervical cancer.
منابع مشابه
COMPARATIVE STUDY OF CHEMORADIATION AND NEOADJUV ANT CHEMOTHERAPY BEFORE RADICAL HYSTERECTOMY IN STAGE m - 1m BULKY CERVICAL CANCER AND WITH TUMOR DIAMETER GREATER THAN 4 CM
Tumor size seems to be a determinant in the prognosis of early cervical cancer. Patients with tumor size greater than 4 cm (bulky) in diameter have worse outcome.' The purpose of this study was to compare the efficacy of preoperative combined chemoradiation and neoadjuvant chemotherapy (NArC) programs followed by radical hysterectomy in stage Ib - lIb bulky cervical cancer. From September ...
متن کاملPivotal roles of snail inhibition and RKIP induction by the proteasome inhibitor NPI-0052 in tumor cell chemoimmunosensitization.
The novel proteasome inhibitor NPI-0052 has been shown to sensitize tumor cells to apoptosis by various chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), although the mechanisms involved are not clear. We hypothesized that NPI-0052-mediated sensitization may result from NF-kappaB inhibition and downstream modulation of the metastasis inducer Snail and t...
متن کاملA New Model for Raf Kinase Inhibitory Protein Induced Chemotherapeutic Resistance
Therapeutic resistance remains the most challenging aspect of treating cancer. Raf kinase inhibitory protein (RKIP) emerged as a molecule capable of sensitizing cancerous cells to radio- and chemotherapy. Moreover, this small evolutionary conserved molecule, endows significant resistance to cancer therapy when its expression is reduced or lost. RKIP has been shown to inhibit the Raf-MEK-ERK, NF...
متن کاملHSV-TK Expressing Mesenchymal Stem Cells Exert Inhibitory Effect on Cervical Cancer Model
A growing area of research is focused on cancer therapy, and new therapeutic approaches are welcomed. Mesenchymal stem cell (MSC)-based gene therapy is a promising strategy in oncology. Intrinsic tropism and migration to tumor microenvironment with off lights are attractive features of this type of cell carrier. In this way, suicide genes have also found a good platform for better performance a...
متن کاملBoth F-18 FDG-avidity and Malignant Shape of Cervical Lymph Nodes on PET/CT after Total Thyroidectomy Predict Resistance to High-dose I-131 Therapy in Patients with Papillary Thyroid Cancer
Objective: Resistance of metastatic lymph nodes (LNs) to high dose I-131 therapy is associated with high morbidity in patients with differentiated thyroid cancer. We evaluated the role of F-18 FDG PET/CT in the prediction of resistance to high dose I-131 therapy in patients with papillary thyroid cancer. Methods: The subjects were 307 patients who underwent total or near total thyroidectomy fol...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 8 شماره
صفحات -
تاریخ انتشار 2013