Oleanonic acid inhibits glioma growth by inactivating STAT3 via upregulating SIRT6 in nude mice
作者机构：Neurosurgery Department of the First Affiliated Hospital of Soochow University Department of Neurosurgery， the Third Affiliated Hospital of Naval Medical University Department of anesthesiology， General Hospital Of Eastern Theater Command Department of Pharmacology， School of Medicine， Shaoxing University
出 版 物：《Food Science and Human Wellness》 (食品科学与人类健康(英文))
年 卷 期：2024年
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：supported by the National Natural Science Foundation of China (No. 81560059 81760058 8160042 31800891)
摘 要：Patients with glioma have a very high mortality rate， thus improving the poor prognosis of glioma has been the goal in the therapeutic field. Searching for more effective drugs for gliomas from natural compounds is a promising strategy. In this study， both oleanonic acid and oleanolic acid inhibited proliferation of glioma cells and reduced expression of cyclin D1 and E1， but the former has a lower IC50 than the latter. Oleanonic acid reduced the expression of p-STAT3 but not p-STAT1 and 5， and also reducing the expression of STAT3 in the nucleus and its transcriptional activity in glioma cells. Furthermore， knockdown of STAT3 expression inhibited proliferation and migration of glioma cells. Next， the expressions of the upstream regulators such as SIRT6 and p-JAK2 but not SIRT1， p-ERK1/2， p300 were increased by oleanonic acid. The overexpression of SIRT6 not only reduced the expression of p-STAT3 and its transcriptional activity but also inhibited the proliferation and migration of glioma cells. In addition， the effects that oleanonic acid reduced the expression of p-STAT3 and its transcriptional activity and inhibited the proliferation and migration were attenuated by the knockdown of SIRT6. Furthermore， oleanonic acid effectively suppressed glioma growth and extended survival in nude mice bearing intracerebral U87 xenografts， but not in nude mice bearing intracerebral SIRT6-knockdown U87 xenografts. In conclusion， oleanonic acid upregulates the expression of SIRT6 to inactivates STAT3 and then inhibits glioma growth.
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