In this study, we described the expression of these three different proteins associated with multidrug resistance and radiotherapy in chordoma. All the tested markers exhibited some changes in their expression pattern in chordoma compared with normal nucleus pulpous. The most prominent reduction in expression was observed for MDR1 which was very weakly expressed or unexpressed in more than 50% of the chordoma samples studied. To our knowledge, this was the first study on genes associated with resistance to chemotherapy and radiotherapy in spinal

chordoma. The current results showed that MRP1 was expressed in the membranous and intracellular regions; HIF-1α was expressed in the cell cytoplasmic and nuclear Selleckchem Regorafenib SGLT inhibitor regions, whereas MDR1 was not expressed in the chordoma tissues or CM-319 cell. ABC multidrug transporters also played an important role in the establishment of important biological barriers such as the placenta, the blood-brain barrier, and the blood-testes barrier. Although the over-expression of these transporters was a common phenomenon in chemoresistant

tumor cells, we found that MRP1 and HIF-1α expression was upregulated in most chordoma tissues in comparison to normal tissues. It had been proposed that upregulation of ABC multidrug transporters in cancers may play a role in tumorigenesis by enhancing exposure of tissues to carcinogenic xenobiotics. Interestingly, the expression of MDR1 was not inversely expressed in the chordoma tissues. New data on HIF-1 signaling and the potential for targeted therapies, including combinations of hormonal therapies for cancer and

selective investigational L-NAME HCl HIF-1α inhibiting small molecules would be discussed. Another mechanism by which hypoxia could increase chemoresistance was to enhance the expression of MDR1 gene via a HIF-1 -dependent regulation [30, 31]. Acknowledgements This work was supported by grants from the National Natural Science Foundation of P. R. China (No. 30873027, No.30973409 and No.30330610) and major issues Foundation of health department in Shaaxi province (No. 2010K13-02-05). The authors thank Dr Lianjia Yang and Ms Yanhua Wen (Orthopadepics Department, Tangdu Hospital, the Fourth Military Medical University, Xi’an, P. R. China) for their pathological diagnosis. We thank Ms Yunyan Liu and Ms Qiong Ma (Orthopadepics Department, Tangdu Hospital, the Fourth Military Medical University, Xi’an, P. R. China) for their skillful technical assistance. We are also grateful to Dr Tongtao Yang, Dr Dianzhong Zhang, Dr Yong Zhou and Dr Minghua Zhang (Orthopadepics Department, Tangdu Hospital, the Fourth Military Medical University, Xi’an, P. R. China) for their Selleckchem Ruxolitinib helpful discussion. References 1. Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH: Chordoma: the nonsarcoma primary bone tumor. Oncologist 2007, 12: 1344–1350.PubMedCrossRef 2.