Abstract：The anti-tumor effects of berberine (BBR) have been confirmed by a large number of studies, among which Akt kinase mediated signaling pathway is the key pathway of BBR anti-tumor research. Its mechanism of action mainly includes mediating cell cycle arrest, inducing mitochondrial apoptosis and autophagy, preventing epithelial mesenchymal transition and angiogenesis, and improving the sensitivity of chemotherapy drugs. Regulation of cancer cell metabolism and improvement of tumor microenvironment. This article reviews the anticancer effect of BBR by targeting Akt kinase, discusses the anti-tumor mechanism of BBR, and promotes the research progress of BBR in the field of clinical anticancer drugs.
刘代利1 王智2 李玲2 张竞飞1 秦汉1 蔡圳2. 小檗碱通过靶向Akt激酶发挥抗癌作用的研究进展[J]. 中国医药导报, 2023, 20(30): 59-62,67.
LIU Daili1 WANG Zhi2 LI Ling2 ZHANG Jingfei1 QIN Han1 CAI Zhen2. Research progress on the anticancer effects of berberine by targeting Akt kinase. 中国医药导报, 2023, 20(30): 59-62,67.
[1] Almatroodi SA，Alsahli MA，Rahmani AH. Berberine：An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways [J]. Molecules，2022， 27（18）：5889. [2] Revathidevi S，Munirajan AK. Akt in cancer：Mediator and more [J]. Semin Cancer Biol，2019，59：80-91. [3] 李娜，张颖，李芳园，等.小檗碱对喉癌细胞克隆、转移及Toll样受体4蛋白的作用[J].世界中医药，2022，17（20）：2867-2872. [4] Wang N，Feng Y，Zhu M，et al. Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells：the cellular mechanism [J]. J Cell Biochem，2010，111（6）：1426-1436. [5] Kou Y，Tong B，Wu W，et al. Berberine improves chemo-sensitivity to cisplatin by enhancing cell apoptosis and repressing PI3K/AKT/mTOR signaling pathway in gastric cancer [J]. Front Pharmacol，2020，11：616251. [6] Hou Q，He WJ，Wu YS，et al. Berberine：A Traditional Natural Product With Novel Biological Activities [J]. Altern Ther Health Med，2020，26（S2）：20-27. [7] Tan HY，Wang N，Tsao SW，et al. Suppression of vascular endothelial growth factor via inactivation of eukaryotic elongation factor 2 by alkaloids in Coptidis rhizome in hepatocellular carcinoma [J]. Integr Cancer Ther，2014，13（5）：425- 434. [8] 谢天飞，王凌云，刘丽，等.小檗碱通过调控PI3K/Akt通路抑制喉癌细胞生长和转移[J].中国新药与临床杂志，2020，39（1）：43-48. [9] Wang Y，Zhang S. Berberine suppresses growth and metastasis of endometrial cancer cells via miR-101/COX-2 [J]. Biomed Pharmacother，2018，103：1287-1293. [10] Gao X，Liu J，Fan D，et al. Berberine enhances gemcitabine-induced cytotoxicity in bladder cancer by downregulating Rad51 expression through inactivating the PI3K/Akt pathway [J]. Oncol Rep，2022，47（2）：33. [11] Wang Y，Liu Y，Du X，et al. Berberine reverses doxorubicin resistance by inhibiting autophagy through the PTEN/Akt/ mTOR signaling pathway in breast cancer [J]. Onco Targets Ther，2020，13：1909-1919. [12] Liu J，Liu P，Xu T，et al. Berberine induces autophagic cell death in acute lymphoblastic leukemia by inactivating AKT/mTORC1 signaling [J]. Drug Des Devel Ther，2020， 14：1813-1823. [13] Xiong RG，Huang SY，Wu SX，et al. Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs：An Update Review [J]. Molecules，2022，27（14）：4523. [14] Li F，Dong X，Lin P，et al. Regulation of Akt/FoxO3a/Skp2 axis is critically involved in berberine-induced cell cycle arrest in hepatocellular carcinoma cells [J]. Int J Mol Sci，2018，19（2）：327. [15] Tak J，Sabarwal A，Shyanti RK，et al. Berberine enhances posttranslational protein stability of p21/cip1 in breast cancer cells via down-regulation of Akt [J]. Mol Cell Biochem，2019，458（1/2）：49-59. [16] Li L，Wang X，Sharvan R，et al. Berberine could inhibit thyroid carcinoma cells by inducing mitochondrial apoptosis，G0/G1 cell cycle arrest and suppressing migration via PI3K-AKT and MAPK signaling pathways [J]. Biomed Phar- macother，2017，95：1225-1231. [17] Zhang Y，Liu X，Yu M，et al. Berberine inhibits proliferation and induces G0/G1 phase arrest in colorectal cancer cells by downregulating IGF2BP3 [J]. Life Sci，2020，260：118413. [18] Chuang TC，Wu K，Lin YY，et al. Dual down-regulation of EGFR and ErbB2 by berberine contributes to suppression of migration and invasion of human ovarian cancer cells [J]. Environ Toxicol，2021，36（5）：737-747. [19] Eo SH，Kim JH，Kim SJ. Induction of G2/M Arrest by berberine via activation of PI3K/Akt and p38 in human chondrosarcoma cell Line [J]. Oncol Res，2014，22（3）：147-157. [20] Chen ZZ. Berberine induced apoptosis of human osteosarcoma cells by inhibiting phosphoinositide 3 Kinase/protein kinase B（PI3K/Akt）signal pathway activation [J]. Iran J Public Health，2016，45（5）：578-585. [21] Saxena S，Shukla S，Kakkar P. Berberine induced modulation of PHLPP2-Akt-MST1 kinase signaling is coupled with mitochondrial impairment and hepatoma cell death [J]. Toxicol Appl Pharmacol，2018，347：92-103. [22] Park GS，Park B，Lee MY. Berberine induces autophagic cell death by inactivating the Akt/mTOR signaling pathway [J]. Planta Med，2022，88（13）：1116-1122. [23] Kou Y，Li L，Li H，et al. Berberine suppressed epithelial mesenchymal transition through cross-talk regulation of PI3K/AKT and RARalpha/RARbeta in melanoma cells [J]. Biochem Biophys Res Commun，2016，479（2）：290-296. [24] Kuo HP，Chuang TC，Tsai SC，et al. Berberine，an isoquinoline alkaloid，inhibits the metastatic potential of breast cancer cells via Akt pathway modulation [J]. J Agric Food Chem，2012，60（38）：9649-9658. [25] Ma W，Zhu M，Zhang D，et al. Berberine inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B2 [J]. Phytomedicine，2017，25：45-51. [26] Kim S，Oh SJ，Lee J，et al. Berberine suppresses TPA-induced fibronectin expression through the inhibition of VEGF secretion in breast cancer cells [J]. Cell Physiol Bioc- hem，2013，32（5）：1541-1550. [27] Cheng HW，Chen YF，Wong JM，et al. Cancer cells increase endothelial cell tube formation and survival by activating the PI3K/Akt signalling pathway [J]. J Exp Clin Cancer Res，2017，36（1）：27. [28] Chen Q，Qin R，Fang Y，et al. Berberine sensitizes human ovarian cancer cells to cisplatin through miR-93/PTEN/Akt signaling pathway [J]. Cell Physiol Biochem，2015，36（3）：956-965. [29] Guo XH，Jiang SS，Zhang LL，et al. Berberine exerts its antineoplastic effects by reversing the Warburg effect via downregulation of the Akt/mTOR/GLUT1 signaling pathway [J]. Oncol Rep，2021，46（6）：8204. [30] Kuo CL，Chi CW，Liu TY. Modulation of apoptosis by berberine through inhibition of cyclooxygenase-2 and Mcl-1 expression in oral cancer cells [J]. In Vivo，2005，19（1）：247- 252.
2023, Vol. 20 
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