Chloroform extract from Sophora Tonkinensis Gagnep. inhibit proliferation, migration, invasion and promote apoptosis of nasopharyngeal carcinoma cells by silencing the PI3K/AKT/mTOR signaling pathway.

Sophora Tonkinensis Gagnep. (STG) has been used as a folk medicine for the treatment of different cancers, especially for nasopharyngeal carcinoma, cervical cancer, liver cancer, stomach cancer, lung cancer and leukemia in China. However, the main chemical composition and anticancer mechanism of chloroform extract of STG (CESTG) were still not very clear. This work was carried out to investigate the anticancer effects and mechanisms of chloroform extract of STG (CESTG) on NPC. Cultured NPC CNE1, CNE2 and Np69 cells were treated with CESTG. Cells were subjected to cell proliferation, colony-forming, migration and invasion assays. Cell cycle and apoptosis were measured by flow cytometry. Western blotting and morphological analysis were also performed. Tumor xenografts and drug treatments were made in BALB/c nude mice. The main compounds of CESTG was separated by HPLC. CESTG inhibited cell viability, clonal growth and induced cell apoptosis in a dose-dependent manner by silencing the PI3K/AKT/mTOR signaling pathway, which is associated with upregulation of cleaved PARP, caspase 3/7/8/9, cleaved caspase 3/7/8/9, Bax and downregulation of PARP, P-PI3K, PI3K, P-AKT, AKT, P-mTOR, mTOR and Bcl-2. In addition, CESTG arrested cell cycle in the G1/S phase, correlating with decreased levels of cyclin D1/B1, CDK 4 and 6. CESTG decreased cell migration and invasion which correlated with decreased expression of β-catenin, vimentin and snail. CESTG significantly inhibited the tumor growth without toxicity. The results presented here suggest that CESTG could be use as a potential source of NPC therapeutic drug.

ShuoWang ，Song Z ，Gong X ，Ou C ，Zhang W ，Wang J ，Yao C ，Qin S ，Yan B ，Li Q ，Wei K ，Hou X ，Zhou X ，Miao J ... -  《-》

Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the Akt/mTOR signaling pathway.

Guo S ，Zhang J ，Wei C ，Lu Z ，Cai R ，Pan D ，Zhang H ，Liang B ，Zhang Z ... -  《-》

Pre-treatment with angiotensin-(1-7) inhibits tumor growth via autophagy by downregulating PI3K/Akt/mTOR signaling in human nasopharyngeal carcinoma xenografts.

Lin YT ，Wang HC ，Chuang HC ，Hsu YC ，Yang MY ，Chien CY ... -  《-》

APLNR is involved in ATRA-induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K-Akt-mTOR signaling.

Liu Y ，Liu Q ，Chen S ，Liu Y ，Huang Y ，Chen P ，Li X ，Gao G ，Xu K ，Fan S ，Zeng Z ，Xiong W ，Tan M ，Li G ，Zhang W ... -  《-》

14-Thienyl methylene matrine (YYJ18), the derivative from matrine, induces apoptosis of human nasopharyngeal carcinoma cells by targeting MAPK and PI3K/Akt pathways in vitro.

Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck cancer with the highest incidence in South China. Previous studies have proved that matrine, a main alkaloid isolated from Sophora flavescens Ait, has antitumor activity against NPC. However, the effect is not so pronounced and the underlying mechanism remains largely unclear. Here we investigated whether 14-thienyl methylene matrine (YYJ18) that was derived from matrine could exert more effective suppression activity on NPC, along with the underlying mechanism. NPC cell lines CNE1, CNE2 and HONE1 were treated with YYJ18. Cell proliferation and apoptosis were determined by MTT assay and flow cytometry. Activation of mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways were determined by Western blotting and quantitative RT-PCR. YYJ18 remarkably inhibited proliferation and induced apoptosis of all three NPC cell lines in a dose-dependent manner, especially in CNE2 cells. Furthermore, YYJ18 treatment significantly suppressed phosphorylation of p38 in CNE2 cells, but upregulated phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and Akt. Next, alterations in downstream signaling were found, including activation of BCL2-associated X protein (Bax), caspase-3 and inactivation of B-cell CLL/lymphoma 2 (Bcl-2). We demonstrate the potent inhibitory effects of 14-thienyl methylene matrine on NPC cells for the first time, which could be mediated by modulation of MAPK and PI3K/Akt pathways.

Xie M ，Yi X ，Wang R ，Wang L ，He G ，Zhu M ，Qi C ，Liu Y ，Ye Y ，Tan S ，Tang A ... -  《-》