The cysteinylLT1 receptor in human renal cell carcinoma

Abstract

The metabolism of arachidonic acid (AA) by either cyclooxygenase or lipoxygenase is believed to play an important role in carcinogenesis. Leukotriene (LT) D4 is a proinflammmatory mediator derived from AA through various enzymatic steps, and 5-lipoxygenase is an important factor in generating LTD4. We investigated LTD4 receptor (cysteinylLT1 receptor, CysLT1R) expression in renal cell carcinoma (RCC), as well as the effect of the CysLT1R antagonist on cell proliferation in the RCC cell line. CysLT1R expression was detected by immunohistochemistry and examined in RCC patients and normal kidney (NK) tissues. The effect of the CysLT1R antagonist on RCC cell growth was examined by MTT assay. Flow cytometry was used to determine whether or not the CysLT1R antagonist induced apoptosis. Initially, only slight CysLT1R expression was detected in NK tissues, and marked CysLT1R expression in RCC tissues. CysLT1R expression was higher in high-grade than in low-grade cancer. Furthermore, the CysLT1R antagonist caused marked inhibition of RCC cells in a concentration- and time-dependent manner through early apoptosis. To conclude, CysLT1R was induced in RCC and the results suggest that the CysLT1R antagonist may mediate the potent anti-proliferative effects of RCC cells. Thus, CysLT1R may become a new target therapy in the treatment of RCC.