ผลของสารเทอริอีนในการยับยั้งการแพร่กระจายและการสร้างหลอดเลือดของเซลล์มะเร็งปอด

บทคัดย่อ

Cancer metastasis is the leading cause of mortality for cancer patients and over seventy percent of lung cancer patients were diagnosed at advanced or metastatic stages resulting in increasing the incidence of mortality. Terrein is a secondary bioactive fungal metabolite that isolated from the Aspergillus terreus. Numerous studies have demonstrated that it has various biological activities including the inhibition of melanogenesis, anti-inflammatory and anticancer properties. In this study, we also analyzed on the anticancer effect of terrein but targeting through the mechanism of metastatic inhibition of lung cancer cells that has never been reported. Human lung cancer cells (A549) were used to determine the cytotoxic effect of terrein compared to normal cell lines Vero, L6 and H9C2 using MTT assay. The results indicated that terrein significantly inhibited cell viability of all of those cells tested with a different level of toxicity which IC50 were at229 ?M, 870 ?M, 1,240 ?M and 579 ?M, respectively. A significant increased cytotoxic effect was clearly observed in A549 cells by LDH assay. The inhibitory effect of terrein on cell proliferation assessed by IncuCyte indicated significantly suppressed A549 cell proliferation. To further investigate the effect of terrein on the migration and invasion processes, both the normal and the aggressive phenotype of A549 grown in the hypoxic conditions were performed. The results revealed that terrein significantly inhibited cancer cell migration and invasion of both normoxia and hypoxia conditions. In terms invasive ability, qPCR demonstrated that terrein decreased MT1-MMP, MMP-2 and MMP-9 expression. This result was supported by a reduction of MMP-2 and MMP-9 activity evaluated by gelatin zymography. Angiogenesis processes of A549 including VEGF secretion, capillary-like tube formation as well as VEGF/VEGFR2 interaction were further determined by ELISA, tube formation assay and western blotting, respectively, which the suppression was indicated. These data were accompanied by a reduction of integrin and FAK protein and its downstream mediators (e.g. PI3K, AKT, mTORC1 and P70S6K). All these data indicate that terrein was able to inhibit all major processes of metastasis in human lung cancer cells, which is crucial for cancer treatment.