Over-expression of these transporters was an adverse prognostic factor in a number of cancers. The significance of the expression of these ABC proteins in chordoma had not yet been reported. Cellular adaptation

to hypoxia was a critical step in tumor mTOR cancer progression [25]. Hypoxia occurred during several pathophysiological processes including tumorigenesis, which was a reduction in the normal level of tissue oxygen tension. Hypoxic cancer cells might undergo a series of genetic and metabolic changes that allowed them not only to survive and proliferate but also to become more resistance to conventional therapies including ionizing radiation and chemical AZD5153 agents. These hypoxic adaptations made the tumors more difficult to treat and confer increased resistance to death from chemotherapy and radiotherapy. In response to hypoxia, cells altered the expression of genes that encoded protein products involved in increasing oxygen

delivery and activated alternate metabolic pathways that did not require oxygen. This hypoxic response was chiefly regulated by HIF-1α. Magnon’s [10] findings supported a crucial role for angiogenesis inhibitors in shifting the fate of radiation-induced HIF-1α activity from hypoxia-induced tumor radioresistance to hypoxia-induced tumor apoptosis. Sullivan [12] determined the effects of hypoxia on multiple forms of drug-induced death in human MDA-MB-231 breast carcinoma cells. These results supported a requirement for HIF-1 in the adaptations leading to drug resistance and revealed that decreased (-)-p-Bromotetramisole Oxalate drug-induced senescence was also an important CX-6258 nmr contributor to the development of hypoxia-induced resistance. Nardinocchi [26] reported that the mechanistic explanation of hypoxia-induced chemoresistance involved upregulation

of HIF-1 pathway and inhibition of the p53 pathway that were partly interconnected by the hypoxia-induced HIPK2 deregulation. They showed for the first time that hypoxia-induced HIPK2 deregulation was counteracted by zinc that restored HIPK2 suppression of HIF-1 pathway and reactivated p53 apoptotic response to drug, underscoring the potential use of zinc supplementation in combination with chemotherapy to address hypoxia and improve tumor treatment. It has been recently reported [27, 28] that the transcription of MDR1 gene was controlled by hypoxia; HIF-1 binding to a putative binding site of human MDR1 promoter was critical for the transcription. Song [29] demonstrated that hypoxia-induced chemoresistance to cisplatin and doxorubicin in NSCLC cells was through the HIF pathway. MDR1 regulation may not be involved in hypoxia-induced chemoresistance. Combining delivery of HIF-1α RNAi lentiviral vector with cisplatin-related chemotherapy regimens could enable us to develop more effective strategy for NSCLC therapy.