Research progress on the role of glutamine metabolism-related proteins in tumor metastasis / 中国癌症杂志

Tumor metastasis is closely related to high mortality rate of cancer.It is well known that glutamine plays an important role in the malignant progression of cancer.Notably,as an important carbon and nitrogen donor,glutamine has been found to be closely related to tumor metastasis in recent years.Glutamine is not only involved in regulating the proliferation of tumor cells,but is also closely related to the migration and invasion of tumor cells.Furthermore,various enzymes along with transporters in the metabolism of glutamine are involved in the process of tumor metastasis through different signaling pathways.This review provided a summary of the role of glutamine in tumor metastasis in recent years and proposed therapeutic targets to provide new strategies for the clinical treatment of tumor metastases.

Gefitinib inhibits glycolysis and induces programmed cell death in non-small cell lung cancer cells / 南方医科大学学报

OBJECTIVE@#To observe the cell death pattern induced by gefitinib in non-small cell lung cancer A549 and H1975 cells and explore the possible mechanism in light of glycolysis.@*METHODS@#The inhibitory effects of gefitinib at 20, 30, or 40 μmol/L in A549 cells and at 20, 40, or 80 μmol/L in H1975 cells were examined using MTT assay. The changes of lactic acid level in the cells were determined with a lactic acid kit, and the expression levels of glycolysis-related proteins (PKM2 and HK2) and the proteins in PI3K-Akt-mTOR signaling pathway were detected using Western blotting. 2-NBDG was used for detecting glucose uptake capacity of the cells, and ATP kit was used to detect the intracellular ATP level. The mitochondrial membrane potential of the cells was examined with the JC-1 kit, and cell apoptosis was analyzed with Annexin V-FITC/PI double staining. The relative expression levels of the apoptotic proteins Bax and Bcl-2 and the autophagy marker protein LC3B were detected with Western blotting.@*RESULTS@#MTT assay showed that gefitinib inhibited the proliferation of A549 and H1975 cells in a time- and dose-dependent manner ( < 0.05). The IC of gefitinib at 24, 48 and 72 h was 48.6, 28.6 and 19.7 μmol/L in A549 cells and was 321.6, 49.1 and 14.6 μmol/L in H1975 cells, respectively. Gefitinib significantly lowered intracellular lactic acid level of the cells ( < 0.05) and down-regulated the expressions of PKM2 and HK2 proteins ( < 0.05) and PI3K-Akt-mTOR signaling pathway-associated proteins ( < 0.05). Gefitinib obviously inhibited glucose uptake and ATP levels in both A549 and H1975 cells ( < 0.05). Treatment with gefitinib induced obviously enhanced apoptosis in the cells, resulting in apoptosis rates of (10.77± 1.0)%, (14.5±0.4)%, (17.4±0.2)% and (32.1±0.6)% at 0, 20, 30 and 40 μmol/L in A549 cells ( < 0.05) and of (10.5±0.6)%, (13.2± 0.92)%, (18.9±0.98)% and (35.1±1.4)% at 0, 20, 40 and 80 μmol/L in H1975 cells, respectively ( < 0.05). The protein expression of Bax increased and that of Bcl-2 decreased following gefitinib treatment in the cells ( < 0.05). Gefitinib significantly increased autophagy in A549 and H1975 cells as shown by increased LC3B expressions following the treatment ( < 0.05).@*CONCLUSIONS@#Gefitinib can inhibit the proliferation, induce apoptosis and increase autophagy in A549 and H1975 cells. Gefitinib induces apoptosis of the cells possibly by affecting glycolysis and PI3K-Akt-mTOR signaling pathway.

Alkaline processing of cantharidin can significanty improve the antitumor activity of cantharidin / 南方医科大学学报

OBJECTIVE@#To assess the changes in the effects of cantharides after alkaline processing on proliferation, migration, invasion, and apoptosis of human lung cancer A549 cells.@*METHODS@#Human non-small cell lung cancer A549 cells were treated with cantharis extract (CTE) from raw cantharides and alkali processed cantharis extract (ACE). The proliferation of the cells was detected with CCK-8 assay, and the cell migration and invasion were assessed using wound healing assay and Transwell assay, respectively. The expressions of MMP1 and MMP2 in the cells were detected using Western blotting, the contents of IFN-γ, IL-1β and TNF-α were measured with ELISA, and cell apoptosis was analyzed with annexinV/PI fluorescent staining.@*RESULTS@#Both CTE and ACE significantly reduced the viability and inhibited the migration of A549 cells, and high-dose ACE produced a significantly stronger inhibitory effect on cell migration than high- dose CTE ( < 0.01). ACE showed more potent inhibitory effect than CTE on the invasion of A549 cells ( < 0.01). Both CTE and ACE inhibited the expressions of MMP1 and MMP2 and up-regulated the level of IFN-γ without significantly affecting the levels of IL-1β and TNF-α. Annexin V/PI staining showed that both CTE and ACE caused apoptosis of A549 cells, but ACE had a stronger proapoptotic effect.@*CONCLUSIONS@#Processing with sodium hydroxide can significantly improve the antitumor activity of cantharides, which inhibits the proliferation, migration and invasion of A549 cells possibly by down-regulating the expressions of MMP1 and MMP2, promoting apoptosis and increasing the level of IFN-γ.