Jinlei Ye, Shilei Wang, Shuo Liu, Ying Chen, Songhai Shen, Qiping Zheng, Zhilei Cui and Lichun Sun
Nasopharyngeal carcinoma (NPC) is a complex epithelial malignancy caused by both internal and environmental factors. Among them, Epstein–Barr virus (EBV) is a definitive etiological factor. The current therapeutic regimen for NPC is far from ideal and recurrence is commonly seen in patients after conventional radio and/or chemotherapy. We have thereby set out to develop new treatments for this deadly disease. Having analyzed a number of nasopharyngeal tissue and cell samples, we found that the level of somatostatin receptors (SSTRs) was positively correlated with EBV infection. Further, SSTR2 is the dominant SSTR isoform expressed in the EBV-positive (EBV (+)) NPC cells, a potential target for precise delivery of therapeutic agents. Cytotoxic effects of small molecule drugs including ansamitocin P-3 (AP-3), camptothecin and colchicine were subsequently evaluated in NPC cells. We found that AP-3 exhibits its strong anti-NPC activities with the IC50 values being 0.07 nM in EBV (+) NPC C666-1 cells and 0.09 nM in EBV (-) NPC CNE2 cells. In the xenograft animal model, AP-3 further shows inhibitory effects on NPC growth. These findings indicated that AP-3’s activity is not related to EBV in NPC cells. Thus, we proposed that SSTR2- specific delivery of AP-3 via linking AP-3 to somatostatin is likely a viable option to treat the EBV (+) NPC patients.
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