Macamides are a class of bioactive natural products obtained from Lepidium meyenii (maca), which have been reported to exert inhibitory activity in cancer. However, their role in lung cancer is currently unknown. In the present study, macamide B was shown to inhibit the proliferation and invasion of lung cancer cells, as determined by Cell Counting Kit-8 and Transwell assays, respectively. By contrast, macamide B induced cell apoptosis, as determined by Annexin V-FITC assay. Moreover, combined treatment with macamide B and olaparib, an inhibitor of poly (ADP-ribose) polymerase, further suppressed the proliferation of lung cancer cells. At the molecular level, the expression of ataxia-telangiectasia mutated (ATM), RAD51, p53 and cleaved caspase-3 were significantly increased by macamide B, as determined by western blotting, whereas the expression levels of Bcl-2 were decreased. By contrast, when ATM expression was knocked down by small interfering RNA technology in A549 cells treated with macamide B, the expression levels of ATM, RAD51, p53 and cleaved caspase-3 were reduced, whereas those of Bcl-2 were increased. Consistently, cell proliferation and invasive ability were partially rescued by ATM knockdown. In conclusion, macamide B inhibits lung cancer progression by inhibiting cell proliferation and invasion, and inducing apoptosis. Furthermore, macamide B may participate in regulating the ATM signaling pathway. The present study provides a potential new natural drug for treating patients with lung cancer.

To elucidate the underlying mechanism of HIF-1α in migration and invasion of choriocarcinoma. Cell proliferation was determined by CCK-8 assay when cell invasion was detected by transwell assay. The protein expression was detected by western blotting, immunohistochemistry, and qPCR assay. HIF-1α was shown to be strongly expressed in both clinical tumour tissues and cell lines in choriocarcinoma. When HIF-1α was efficiently knocked down in JEG3 cells, the proliferation rate was reduced by approximately 50

Lung cancer causes thousands of deaths worldwide every year, and present therapeutics show little benefit for advanced-stage patients. Researchers do not know why and how lung cancer begins. Lactamase β (LACTB) is a tumor-suppressor in some cancers. However, its role in lung cancer is unknown. By analyzing the TCGA database and Kaplan-Meier Plotter database, LACTB was found to be downregulated in lung cancer tissues but the methylation level was increased. Patients with high LACTB expression exhibited improved survival. Then, in vitro assays demonstrated that LACTB overexpression inhibited cell migration and invasion, and induced apoptosis in H1299 and H1975 cells. Knockdown of LACTB caused the reverse effects. Moreover, a much higher apoptotic rate and more potent inhibitory effects on H1299 and H1975 cells were obtained when LACTB was combined with docetaxel. In addition, members of the epithelial-mesenchymal transition (EMT) signaling pathway were assessed using western blot analysis. The expression of E-cadherin was decreased while levels of N-cadherin and vimentin were increased after knockdown of LACTB in lung cancer cells. By contrast, overexpression of LACTB increased the level of E-cadherin but decreased N-cadherin and vimentin. Therefore, LACTB is a tumor suppressor in lung cancer that inhibits cell migration and invasion and induces cell apoptosis. Meanwhile, LACTB was found to strengthen the anticancer role of docetaxel and to suppress the EMT pathway in lung cancer.

Liver cancer is a malignant disease and causes thousands of death each year. The prognosis is dismal for patients with metastasis and recurrence. It is urgent to disclose the cause and mechanism underlying liver cancer. LARGE1 encodes a glycosyltransferase and was reported to promote progression in cancer. But its role in liver cancer is unknown. In this study, LARGE1 displayed upregulated expression in liver cancer cells. When LARGE1 was knocked down in SMMC-7721 and Huh-7 cells, the ability of cell proliferation and colony formation were decreased significantly. Cell migration and invasion were suppressed. The number of cells in G1 phase increased but decreased in S phase. Cell apoptosis was not affected. Tumor growth in vivo was also inhibited. Tumor volume was decreased from 1270 mm3 to 721 mm3 (p < 0.05) and tumor weight from 0.95 g to 0.63 g (p < 0.05). Furthermore, the expression of β-catenin, TCF and Cyclin D1 was reduced when LARGE1 was knocked down but increased in LARGE1-overexpressed cells. LGK-974, a specific inhibitor in canonical Wnt signaling, inhibited cell proliferation even when LARGE1 was over-expressed. In tumor tissues, LARGE1 was increased by 4.8 folds compared to paratumoral tissues. And higher LARGE1 expression caused shorter survival. Clinicopathological analysis demonstrated that LARGE1 was associated with TNM stage (Ⅰ/Ⅱ vs III/IV, p = 0.005). Therefore, LARGE1 promotes progression and regulates Wnt/β-catenin signaling pathway in liver cancer.

PURPOSE:Evidence indicates that the actin-binding protein Coronin 3, which is aberrantly expressed in various cancers, is associated with cancer development and progression. However, little is known about the role of Coronin 3 in glioma tumorigenesis. Here, we aimed to explore the biological function and regulatory mechanism of Coronin 3 in glioblastoma (GBM).MATERIALS AND METHODS:Coronin 3 level in human GBM clinical samples and cell lines was investigated. The shRNA knockdown strategy was used to assess the tumor characteristics of GBM cell lines. The role of β-catenin in Coronin 3-mediated oncogenic phenotypes was evaluated.RESULTS:Coronin 3 was found to be highly upregulated in glioma cell lines. Furthermore, knockdown of Coronin 3 significantly inhibited the growth of glioma cells both in vivo and in vitro and suppressed the expression of Wnt/β-catenin pathway genes, including β-catenin, Cyclin D1, and c-Myc. Moreover, we demonstrated that Coronin 3 regulates the expression of β-catenin in glioma. Our results revealed that Coronin 3-stimulated tumor growth was β-catenin-dependent.CONCLUSION:Our study reveals a new molecular mechanism of Coronin 3 in promoting glioma growth and development through regulating the Wnt/β-catenin signaling pathway.

The immunological mechanism mediated by T cells is the main therapeutic target in the treatment of renal cell carcinoma (RCC) with interleukin (IL)-2 and interferon (IFN)-α. The aim of the present study was to evaluate the role of B7-H4 in the IL-2, IFN-α and IFN-γ treatment of clear cell RCC (ccRCC). A total of 154 paraffin-embedded ccRCC tissues were studied using immunohistochemistry, which subsequently indicated that positive B7-H4 expression is associated with adverse clinical features in ccRCC. The effects of IL-2, IFN-α and IFN-γ on B7-H4 expression in a ccRCC cell line were evaluated at the mRNA and protein levels. In addition, the effect of B7-H4 on the killing activity of T cells was detected. B7-H4 expression was identified to be upregulated by IL-2, IFN-α and IFN-γ, of which, IFN-γ was the most capable. Additionally, blocking of B7-H4/B7-H4 ligand interactions may rescue the killing activity of T cells. Altogether, the observations of the current study showed that the immune escape pathway induced by B7-H4 may be one of the most important reasons for the low efficacy of IL-2 and IFN-α and the inability to observe the efficacy of IFN-γ in mRCC. This indicates that B7-H4 may be used as a new molecular biology marker to select treatment options for patients with ccRCC.