Chen Yuan-Min, Tang Bi-Xia, Chen Wei-Yong, Zhao Ming-Sheng
Department of Nephrology, The Seventh People's Hospital of Chengdu, Chengdu, Sichuan 610000, P.R. China.
Oncol Lett. 2020 Nov;20(5):170. doi: 10.3892/ol.2020.12027. Epub 2020 Aug 28.
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.
肾细胞癌是泌尿系统常见的恶性肿瘤。熊果酸（UA）在某些类型的癌症中发挥重要的抗肿瘤作用，如肺癌、乳腺癌和肝细胞癌；然而，据我们所知，UA对肾癌的影响尚未得到研究。在本研究中，将A498细胞用不同浓度的UA处理12、24和48小时，然后加入NLR家族含pyrin结构域3（NLRP3）受体的抑制剂MCC950来阻断NLRP3信号传导。使用MTS试验分析A498细胞的增殖情况，使用Transwell试验分析侵袭性。通过蛋白质印迹法检测NLRP3、裂解的半胱天冬酶-1、白细胞介素-1β和基质金属蛋白酶-2的表达水平。目前的结果表明，UA处理后A498细胞的侵袭性显著降低（P<0.05），而NLRP3、裂解的半胱天冬酶-1和白细胞介素-1β的表达水平显著升高，且UA刺激后基质金属蛋白酶-2的表达降低（P<0.05）。MCC950处理可逆转这种情况（P<0.05），NLRP3除外。总之，目前的结果表明，暴露于UA可降低A498细胞的增殖和侵袭性。此外，暴露于UA显著降低基质金属蛋白酶-2的产生并诱导NLRP3炎性小体的激活，这被MCC950处理所逆转，表明NLRP3激活可能参与UA对A498细胞侵袭性的抑制作用。
