[The role and the molecular mechanism of abietic acid in the proliferation, invasion and migration of cisplatin-resistant nasopharyngeal carcinoma cells].

Objective:To investigate the effects and molecular mechanisms of abietic acid in the cell proliferation, invasion and migration of cisplatin-resistant nasopharyngeal carcinoma cells. Methods:①Cisplatin-resistant C666/DDP cell line was constructed by increasing drug concentration method. ②The effects of abietic acid on proliferation, invasion and migration of C666/DDP cells were investigated by CCK-8 method, reactive oxygen species（ROS） and mitochondrial membrane potential（MMP） level assay and subcutaneous tumorigenesis assay in nude mice to detect the effects of abietic acid on proliferation and apoptosis of C666/DDP cells in vitro and in vivo. The effect of abietic acid on the proliferation and apoptosis of C666/DDP cells in vitro and in vivo was measured by Transwell assay. ③Western blot and IHC method to detect the expression of PI3K/AKT/mTOR pathway related proteins. Results:①The IC50 of cisplatin cytotoxicity to C666-1 was about 25 µmol/L. RI=25 µmol/L /4 µmol/L=6.25, resistance was obtained, and the C666-1-DDP resistant strain was successfully constructed. ②Abietic acid promoted apoptosis and inhibited proliferation of C666/DDP cells, and showed G2/M phase block; transwell showed that abietic acid inhibited C666/DDP cell migration and invasion, increased ROS level of C666/DDP cells and decreased MMP. Transwell showed that abietic acid inhibited the migration and invasion ability of C666/DDP cells, increased the ROS level of C666/DDP cells and decreased MMP. ③Animal experiments showed that abietic acid inhibited the proliferation of cisplatin-resistant nasopharyngeal carcinoma in vivo in a concentration gradient and suppressed the expression of PI3K/AKT/mTOR signaling pathway-related proteins. Conclusion:Abietic acid inhibits proliferation, invasion and migration of cisplatin-resistant nasopharyngeal carcinoma cells by a mechanism related to inhibition of PI3K/AKT/mTOR signaling pathway.

m6A modification-mediated BATF2 suppresses metastasis and angiogenesis of tongue squamous cell carcinoma through inhibiting VEGFA.

The aim is to explore the underlying mechanism of basic leucine zipper ATF-like transcription factor 2 (BATF2) in tongue squamous cell carcinoma (TSCC). The expression of BATF2 in TSCC tissues and corresponding adjacent normal TSCC tissues, human TSCC cell lines (SCC-15 and CAL-27) and human normal tongue epithelial cells NTEC was detected. Then, SCC-15 cells with stable BATF2 knockdown and CAL-27 cells with BATF2 overexpression were established to investigate the functional effect of BATF2 on TSCC. Thereafter, the effect of BATF2 on TSCC angiogenesis and BATF2 m6A methylation was also examined. BATF2 was significantly downregulated in TSCC tissues and cell lines, and BATF2 overexpression could suppress growth, metastasis and angiogenesis of TSCC. Mechanistically, vascular endothelial growth factor A (VEGFA) was identified as a downstream gene of BATF2, and it was confirmed that BATF2 suppressed growth, metastasis and angiogenesis of TSCC via inhibiting VEGFA. In addition, the N6-methyladenosine (m6A) modification of BATF2 mRNA mediated by METTL14 suppressed its expression in TSCC. METTL14/BATF2 axis could serve as a novel promising therapeutic candidate against angiogenesis for TSCC.