Ursolic acid inhibits the invasiveness of A498 cells via NLRP3 inflammasome activation

熊果酸通过激活NLRP3炎症小体抑制A498细胞侵袭

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作者:Yuan-Min Chen, Bi-Xia Tang, Wei-Yong Chen, Ming-Sheng Zhao

Abstract

Renal cell cancer is a common malignant tumor of the urinary system. Ursolic acid (UA) serves an important antitumor role in certain types of cancer, such as lung cancer, breast cancer and hepatocellular carcinoma; however, to the best of our knowledge, the effect of UA on renal cancer has not yet been investigated. In the present study, A498 cells were treated with different concentrations of UA for 12, 24 and 48 h, and then MCC950, an inhibitor of the NLR family pyrin domain-containing 3 (NLRP3) receptor, was added to block NLRP3 signaling. The proliferation of A498 cells was analyzed using an MTS assay and invasiveness was analyzed using a Transwell assay. The expression levels of NLRP3, cleaved caspase-1, IL-1β and MMP-2 were detected using western blotting. The present results demonstrated that the invasiveness of A498 cells was significantly decreased following UA treatment (P<0.05), while expression levels of NLRP3, cleaved caspase-1 and IL-1β were significantly increased, and MMP-2 expression was decreased following UA stimulation (P<0.05). This was reversed by MCC950 treatment (P<0.05), with the exception of NLRP3. In conclusion, the present results indicated that UA exposure decreased the proliferation and invasiveness of A498 cells. Additionally, UA exposure significantly decreased MMP-2 production and induced the activation of NLRP3 inflammasome, which was reversed by MCC950 treatment, indicating that NLRP3 activation may be involved in UA inhibition of A498 cell invasiveness.

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