Targeting TGF-ß1 and AKT signal on growth and metastasis of anaplastic thyroid cancer cell in vivo.

The article "Targeting TGF-ß1 and AKT signal on growth and metastasis of anaplastic thyroid cancer cell in vivo, by Y. Li, D. Chen, F.-Y. Hao, K.-J. Zhang, published in Eur Rev Med Pharmacol Sci 2016; 20 (12): 2581-2587. PMID: 27383308" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/11013.

Targeting TGF-ß1 and AKT signal on growth and metastasis of anaplastic thyroid cancer cell in vivo.

OBJECTIVE: We have recently reported that therapies targeting TGF-ß1 signaling were effective to prevent the anaplastic thyroid cancer (ATC) cell growth, but not the invasion. Phosphatidylinositol 3-kinase (PI3K)/AKT signaling are activated in ATC and play a major role in ATC invasion. Herein, we examined the effects of targeting TGF-ß1 by shRNA in combination with pan-AKT inhibitor, MK-2206 on growth and metastasis of ATC xenografts implanted in severe combined immunodeficient mice. MATERIALS AND METHODS: 8505C cells or 8505C/shRNA cells or 8505C/TGF-ß1 shRNA cells were implanted sc in 5-week-old female nude mice. Upon establishment of palpable tumours, MK-2206 was administered at 60 mg/kg, orally, three times a week for 6 weeks. RESULTS: The results showed that TGF-ß1/shRNA alone only prevents anaplastic thyroid cancer (ATC) tumor formation, but not lung metastasis. MK-2206 alone only inhibits lung metastasis, but not tumor formation. The combined treatment with TGF-ß1/shRNA and MK-2206 led to an approximately 71% growth inhibition compared with TGF-ß1/shRNA (44%) and MK-2206 (15%). The combined treatment with TGF-ß1/shRNA and MK-2206 significantly inhibits lung metastasis. CONCLUSIONS: These findings demonstrated that targeting TGF-ß1 in combination with MK-2206 was the effective method for treatment of ATC.

Capillarisin Exhibits Anticancer Effects by Inducing Apoptosis, Cell Cycle Arrest and Mitochondrial Membrane Potential Loss in Osteosarcoma Cancer Cells (HOS).

The aim of the present study was to assess the anticancer activity of capillarisin against human osteosarcoma (HOS) cancer cells in vitro. Cell viability after capillarisin drug treatment and evaluated by MTT assay. The extent of cell death induced by capillarisin was estimated by using lactate dehydrogenase (LDH) assay. The effect of capillarisin on cell cycle phase distribution and mitochondrial membrane potential (ΛΨm) was demonstrated via flow cytometry using propidium iodide (PI) and rhodamine-123 (Rh-123) DNA-binding fluorescent dyes respectively. Fluorescence microscopy was employed to examine the morphological changes in osteosarcoma cancer cells and presence of apoptotic bodies following capillarisin treatment. The results of this study revealed that capillarisin induced dose-dependent growth inhibition of these cancer cells after 12-h of incubation. Further, capillarisin induced significant release of LDH from these cell cultures and this LDH release was much more noticeable at higher concentrations of capillarisin. Hoechst 33258 staining revealed characteristic morphological features of apoptosis triggered by capillarisin treatment. Cell cycle analysis revealed that capillarisin induced dose-dependent G0/G1-phase cell cycle arrest. Capillarisin also trigerred a progressive and dose-dependent reduction in the mitochondrial membrane potential. In conclusion, capillarisin inhibits cancer cell growth of osteosarcoma cells by inducing apoptosis accompanied with G0/G1-phase cell cycle arrest and loss in mitochondrial membrane potential.

Group IIa secretory phospholipase A2 (sPLA2IIa) and progression in patients with lung cancer.

OBJECTIVE: Group IIa secretory phospholipase A2 (sPLA2 IIa) plays a role in the malignant potential of several epithelial cancers. It is overexpressed in many cancer specimens and its elevated levels are correlated with high tumor grade and metastasis. Here, we evaluate the clinical significance of sPLA2 IIa in lung adenocarcinoma and the role of sPLA2 IIa in the process of cancer cell invasion and metastasis. PATIENTS AND METHODS: Immunohistochemistry was used to investigate sPLA2 IIa in surgically resected lung adenocarcinoma of 180 patients and its correlation with survival. We overexpressed sPLA2 IIa in a lung adenocarcinoma cell line with very low sPLA2 IIa levels and investigated the in vitro and in vivo effects of sPLA2 IIa expression. RESULTS: High expression of sPLA2 IIa in lung cancer tissue was significantly associated with clinical stage, metastasis, postoperative relapse and shorter patient survival. The overexpression of sPLA2 IIa enhanced xenograft tumor growth and invasion in vitro. CONCLUSIONS: sPLA2 IIa expression can predict the clinical outcome of lung adenocarcinoma patients. sPLA2 IIa is a novel invasion-promoting gene in lung adenocarcinoma.

Cluster of differentiation 24 monoclonal antibody induces apoptosis in the osteosarcoma cells.

OBJECTIVES: Cluster of differentiation 24 (CD24) was overexpressed in osteosarcoma and positive CD24 expression correlates significantly with distant metastasis invasion and poor survival in osteosarcomas. We, therefore, suggested that CD24 would be a new molecular target for therapeutic strategies. In the present study, we aimed to investigate the effects of CD24 down-regulation using monoclonal antibodies (mAb) on apoptosis in osteosarcoma cells in vitro and in vivo. MATERIALS AND METHODS: Osteosarcoma MG-63 cells were treated with Anti-CD24 mAb, and the effects on growth and apoptosis were evaluated in vitro and in vivo. RESULTS: Anti-CD24 mAb could induce the apoptosis of cultured MG63 cells and anti-CD24 mAb treatment inhibited the tumor growth after cancer cell grafting and enhanced the cell apoptosis inside the tumor tissue. CONCLUSIONS: The findings showed that anti-CD24 mAb targeting therapy provides a new avenue toward treating osteosarcoma.