Background: Sanghuangporus vaninii has antioxidant, anti-inflammatory, anti-tumor and other effects. However, the antitumor effects and mechanisms of S.vaninii gainst pancreatic cancer remain unclear. Methods: The antitumor activity of compounds isolated from S. vaninii was evaluated, and cell function experiments, such as wound healing, transwell and 3D culture assays, were conducted after the target cancer species was determined. Transcriptome analysis, Micro-Scale Thermophoresis and western blot were used to verify the targets and signaling pathways. Results: 13 compounds were isolated and identified from S.vanini. Among them, compound 1, the phenylpentane derivative compound, has the strongest inhibitory activity on the pancreatic cancer cells. In vitro, compound 1 inhibited the proliferation, migration, invasion, tube formation and colony formation of PANC-1 cells in a dose-dependent manner. Through transcriptome analysis, the signaling pathways compound 1 targeted were identified as MAPK/PI3K and HIPPO pathways. Western blot and immunofluorescence assay also showed that compound 1 can inhibit the EMT through inactivated HIPPO signaling pathway. By molecular docking and MST assay, we confirmed that compound 1 interacted with EGFR by binding with LYS745/PHE856 of EGFR. After knocking down EGFR, the effect of compound 1 on downstream signaling pathways was weakened, and the functions such as migration and invasion of cancer cells were also decreased. Conclusion: Compound 1, the phenylpentane derivative isolated from S. vaninii, inhibited the malignant process and EMT in PANC-1 cells via MAPK/PI3K and HIPPO signaling pathways by targeting EGFR. These data indicated that compound 1 might be a potential drug candidate for pancreatic cancer treatment.

Background and Purpose Hepatocellular carcinoma has high ability of vascular invasion and metastasis. Vasculogenic mimicry (VM) is closely related to the metastasis and recurrence of hepatocellular carcinoma (HCC). According to previous research, Chloranthus henryi has anti-tumor effect, but its molecular mechanism in the treatment of HCC has not yet been stated. In our study, we aimed to investigate the effect of the extract of Chloranthus henryi in HCC and its target and molecular mechanism. Experimental Approach In this study, we isolated a chalcone compound from Chloranthus henryi, compound 4, identified as flavokawain A (FKA). We determined the anti-HCC effect of FKA by MTT and identified the target of FKA by molecular docking and CETSA. Hepatoma cells proliferation, migration, invasion, and VM formation were examined using EDU, wound healing, transwell, vasculogenic mimicry, and IF. WB, RT-PCR, and cell transfection were used to explore the mechanism of FKA on hepatoma cells. Tissue section staining is mainly used to demonstrate the effect of FKA on HCC in vivo. Key Results We confirmed that FKA can directly interact with CXCL12 and HCC proliferation, migration, invasion, and VM formation were all inhibited through reversing the EMT progress in vitro and in vivo through the PI3K/Akt/NF-κB signaling pathway. Additionally, by overexpressing and knocking down CXCL12, we got the same results. Conclusion and Implications FKA attenuated proliferation, invasion and metastatic and reversed EMT in HCC via PI3K/Akt/HIF-1α/NF-κB/Twist1 pathway by targeting CXCL12. This study proposed that FKA may be a candidate drug and prospective strategy for HCC therapy.