%0 Journal Article
%T Beyond the Limits of Oxygen: Effects of Hypoxia in a Hormone-Independent Prostate Cancer Cell Line
%A A. C. Mamede
%A A. M. Abrantes
%A L. Pedrosa
%A J. E. Casalta-Lopes
%A A. S. Pires
%A R. J. Teixo
%A A. C. Gon£¿alves
%A A. B. Sarmento-Ribeiro
%A C. J. Maia
%A M. F. Botelho
%J ISRN Oncology
%D 2013
%R 10.1155/2013/918207
%X Prostate cancer (PCa) has a high incidence worldwide. One of the major causes of PCa resistance is intratumoral hypoxia. In solid tumors, hypoxia is strongly associated with malignant progression and resistance to therapy, which is an indicator of poor prognosis. The antiproliferative effect and induced death caused by doxorubicin, epirubicin, cisplatin, and flutamide in a hormone-independent PCa cell line will be evaluated. The hypoxia effect on drug resistance to these drugs, as well as cell proliferation and migration, will be also analyzed. All drugs induced an antiproliferative effect and also cell death in the cell line under study. Hypoxia made the cells more resistant to all drugs. Moreover, our results reveal that long time cell exposure to hypoxia decreases cellular proliferation and migration. Hypoxia can influence cellular resistance, proliferation, and migration. This study shows that hypoxia may be a key factor in the regulation of PCa. 1. Introduction Prostate cancer (PCa) is one of the most common diseases in the world, being the sixth leading cause of cancer death worldwide [1]. The incidence of PCa varies according to three major risk factors: age, ethnicity, and familial predisposition [2¨C6]. Hypoxia can be defined as a reduction in oxygen partial pressure (pO2). This characteristic constitutes a condition of various pathophysiological states such as ischemic vascular disease, myocardial infarction, stroke, respiratory insufficiency, and cancer [7]. Clinically relevant levels of hypoxia are detected in 50% to 60% of solid tumors [8]. Hypoxia results from an imbalance between rate of consumption and supply of oxygen to cancer cells, thus compromising several cellular functions. Cancer cells have the capacity to adapt to hypoxic environments due to various genetic and epigenetic mechanisms and alterations at cellular level that contribute to adaptive changes which lead to a clinically aggressive phenotype, having hypoxic tumors a poor prognosis. These tumors are more difficult to treat, being highly resistant, presenting an increased risk of recurrence and progression [9, 10]. Regarding PCa, intratumoral oxygen levels were evaluated through a polarographic electrode with the form of a needle, and it was found that pO2 in PCa was significantly lower (pO2 = 2.4£¿mmHg) than in normal tissues (muscle, pO2 = 30£¿mmHg) [11]. In fact, increase of hypoxia may be critical in PCa progression and resistance [12]. In this work, we aim at studying the antiproliferative effect and cell death induced by various agents of chemotherapy and hormonal
%U http://www.hindawi.com/journals/isrn.oncology/2013/918207/