Network Analysis and Basic Experiments on the Inhibition of Renal Cancer Proliferation and Migration by Alpinetin through PI3K/AKT/ mTOR Pathway

作者全名："Guo, Yu; Jiang, Li; Luo, Shengjun; Hu, Daixing; Zhao, Xin; Zhao, Guozhi; Tang, Wei"

作者地址："[Guo, Yu; Jiang, Li; Luo, Shengjun; Hu, Daixing; Zhao, Xin; Zhao, Guozhi; Tang, Wei] Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing 400000, Peoples R China"

通信作者："Tang, W (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing 400000, Peoples R China."

来源：CURRENT MOLECULAR MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001134303500001

JCR分区：Q3

影响因子：2.2

年份：2023

卷号：24

期号：1

开始页：134

结束页：144

文献类型：Article

关键词：Proliferation; alpinetin; clear cell renal cell carcinoma; migration; PI3K/Akt/mTOR; PI3K/Akt pathway

摘要："Background: Alpinetin, a natural flavonoid, has been shown to have anticancer effects on many tumors. This study investigated the antitumor effect of alpinetin on renal clear cell carcinoma (ccRCC).Methods: Network Pharmacology analysis was carried out on the targets and molecular mechanisms of alpinetin treating ccRCC. The Annexin V PE/7-AAD kit was used to detect apoptosis. Flow cytometry and Cell Counting Kit-8 (CCK-8) were used to detect cell proliferation and cycle. A 24-well transwell chamber and the ibidi scratch insertion performed cell migration analysis. The protein expression of the target molecule was detected by Western blotting. Nude mouse tumorigenesis assays were used to determine the in vivo antitumor effects of alpinetin.Results: The network pharmacology revealed that GAPDH, HRAS, SRC, EGFR, and AKT1 are the main targets of alpinetin in treating ccRCC, with the PI3K/AKT signaling pathway being the main pathway of action. We found that alpinetin could significantly inhibit the proliferation and migration of ccRCC cells by inducing apoptosis. In addition, alpinetin also inhibited the cycle progression of ccRCC cells by blocking them in the G1 phase. Furthermore, in vivo and in vitro, alpinetin could inhibit the activation of an important pathway involved in the proliferation and migration of ccRCC cells, namely the PI3K/Akt pathway.Conclusion: Alpinetin can inhibit the growth of ccRCC cells by inhibiting the activation of the PI3K/Akt pathway and can be a potential anti-cancer drug for ccRCC."

基金机构：Incentive plan for scientific institutions of Chongqing [jxyn2021-1-20]

基金资助正文："This work was supported by an incentive plan for scientific institutions of Chongqing, Fund No. jxyn2021-1-20."