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AIM To compare the anti-cancer effects of furanodiene and β-elemene in human lung cancer cells and to explore the effects and mechanisms when combined treatment of furanodiene and paclitaxel.METHODS MTT assay and flow cytometry were used to detect the anti-proliferative effects and cell cycle distribution, respectively.Real-time PCR was used to show the mRNA levels of the related molecules.Western blot assay and immunocytochemical labeling were used to detect the expression and localization of proteins, respectively.RESULTS Furanodiene concentration-dependently inhibited the cell proliferation of A549, NIH-H1299, and 95-D lung cancer cells.β-Elemene, another terpenoid isolated from Rhizoma Curcumae, exhibited weaker anti-proliferative effects in A.549 and NIH-H1299 cells and activities similar to furanodiene in 95-D cells.Combined treatment of furanodiene with paclitaxel showed synergetic activity in NIH-H1299 and 95-D cells.Compared with the treatment of paclitaxel alone in 95-D cells, the combined treatment reduced the mitotic phase cells while increased G1 phase cells.In the group of combined treatment, the protein levels of cyclin D1, full-PARP, pro-caspase 3, pro-caspase 7 and Bcl-2 were down-regulated while those of p-p53 and Bax were up-regulated as compared with the treatment of furanodiene or paclitaxel alone.Interestingly, combined treatment did not increase the protein levels of endoplasmic reticulum stress-related proteins, such as binding immunoglobulin protein (BIP) and C/EBP homologous protein (CHOP), though the mRNA and protein levels of these molecules and the accumulation of CHOP in the nucleus were significantly up-regulated after furanodiene treatment.Furthermore, the protein levels of integrin β4, paxillin and FAK were also obviously down-regulated in the combined treatment group.CONCLUSION Furanodiene has considerable anti-cancer proliferation capacity compared with that of β-elemene in vitro.Combined treatment of furanodiene with paclitaxel showed synergetic anti-cancer activity which may affect several cellular signaling pathways.