Abstract
The eukaryotic translation initiation factor 3a (eIF3a) is one of the core subunits of the translation initiation complex eIF3, responsible for ribosomal subunit joining and mRNA recruitment to the ribosome. Our previous study identified that it was correlated with platinum response in lung cancer. The current study aims to test the hypothesis that eIF3a may affect the drug response and prognosis of ovarian cancer patients receiving platinum-based chemotherapy by regulating xeroderma pigmentosum complementation group C (XPC) and p27(Kip1). Immunohistochemistry and western blot was used to determine the expression of eIF3a in 126 human ovarian cancer tissues followed by association analysis of eIF3a expression with patient's response and survival. Ectopic over-expression and RNA interference knockdown of eIF3a were carried out in A2780/cisplatin (DDP) and its parental A2780 cells, respectively, to determine the effect of altered eIF3a expression on cellular response to cisplatin by employing MTT assay. Western Blot analyses were also carried out to determine the regulation of eIF3a on XPC and p27(Kip1). eIF3a expression was associated with response of ovarian cancer patients to DDP-based chemotherapy and their survival. Overexpression and knockdown of eIF3a increased and decreased the cellular response to cisplatin in A2780/DDP and A2780 cells, respectively. In addition, XPC and p27(Kip1) were down regulated by eIF3a. eIF3a improves ovarian cancer patients' response to DDP-based chemotherapy via down regulating XPC and p27(Kip1).
Highlights
Epithelial ovarian cancer (EOC) is one of the most common gynecologic malignancies, and the fifth most frequent cause of death by cancer in women in the United States [1]
We explored the association of eukaryotic translation initiation factor 3a (eIF3a) expression with chemotherapy response, the results were summarized in Table 1. eIF3a staining did not appear to have any significant correlation with the age and histologic type listed in the table
We found that eIF3a was highly expressed in DDP sensitive EOC patients compared with DDP resistance EOC patients, and higher eIF3a expression patients have better prognosis
Summary
Epithelial ovarian cancer (EOC) is one of the most common gynecologic malignancies, and the fifth most frequent cause of death by cancer in women in the United States [1]. In China, EOC is one of the top 10 most commonly cancers in the female population. In spite of high response rates to the standard first-line treatment for advanced disease with primary debulking surgery, followed by cisplatin (DDP)-based chemotherapy, more than 70% of the patients eventually relapse developing drug-resistant disease [3]. Patients may respond firstly to the therapy, the cancer often becomes resistant to further chemotherapy, at this point, the number of effective treatment options is limited. For EOC, clinically useful markers that identify DDP resistant tumors among the overall high number of chemosensitive patients, remains a critical need. DDP resistant EOC patients could benefit from alternate and/or additional therapeutic options www.impactjournals.com/oncotarget in first-line therapy. Reliable early identification of DDP resistance may allow the development of clinical trials targeting this population with novel alternate therapies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
