SMAC exhibits anti-tumor effects in ECA109 cells by regulating expression of inhibitor of apoptosis protein family

BACKGROUND The poor prognosis and rising incidence of esophageal cancer highlight the need for improved therapeutics that are essential prior to treatment.LCL161 is an SMAC(second mitochondrial activator of caspases)mimic and inhibitor of apoptosis protein(IAP)antagonist which exhibits anti-tumor effects and improves the chemical sensitivity of many cancers.AIM To ascertain the effects and mechanisms of the SMAC analog LCL161 on esophageal cancer cells.METHODS MTT assay and TUNEL assay were used to detect cell proliferation and apoptosis,respectively.Western blot analysis was used to study the molecular mechanisms of LCL161-induced death of ECA109 cells.RESULTS LCL161 decreased ECA109 cell proliferation in dose-and time-dependent manner and induced apoptosis of ECA109 cells in a dose-dependent manner.Also,LCL161 induced a significant decrease in the expression of the XIAP and significant increase in the expression of Caspase-3.In addition,Bax increased significantly with increasing concentrations of LCL161,and the relative expression of Bax was significantly different between groups.CONCLUSION These findings support the hypothesis that LCL161 can inhibit proliferation and induce apoptosis in esophageal cancer cells by regulating the expression of IAP family members,suggesting that it has potential to be an effective treatment for esophageal squamous cell carcinoma.

Tonglian Decoction(通莲汤)Arrests the Cell Cycle in S-phase by Targeting the Nuclear Factor-Kappa B Signal Pathway in Esophageal Carcinoma Eca109 Cells

Objective： To investigate the anti-tumor activity and molecular mechanism of Tonglian Decoction （通莲汤, TLD） on esophageal carcinoma Eca109 cells. Methods： Ecal09 cells were treated with TLD and its separated formulae, including the clearing-heat and detoxification formula （Q）, activating-blood and promoting-qi formula （H） and nourishing-yin and blood formula （Z）. Cell proliferation was measured using the 3-（4,5-dimethyl-2- thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide assay, cell morphology was observed using a microscope, the cell cycle was measured using flow cytometry and the activity of the nuclear factor-kappa B （NF- K B） signal pathway was detected by Western blot. Results： The half maximal inhibitory concentrations of TLD, Q and H were 386, 771 and 729 rag/L, respectively. TLD, Q and H significantly inhibited cell proliferation, with 69.43%, 60.84% and 61.90% of treated cells in the G1 phase of the cell cycle. The percentage of cells in S phase increased significantly after treatment with TLD, Q, and H compared with the control group （P〈0.05）, and TLD showed the strongest effect. Z had no influence on the cell cycle compared with the control group （P〉0.05）. Western blot detection indicated slight differences in the inhibition of the NF- K B pathway by the different formulae. TLD formula strongly inhibited IKK β, NF- K B, interleukin-6 and tumor necrosis factor-α expression compared with the control group. Conclusions： TLD inhibited Eca109 cell proliferation by arresting cells in S phase. The possible mechanism might be related to inhibiting the NF- K B transduction cascade. The combination of the herbs found in the three separate formulae, H, Q and Z, work synergistically in TLD to produce the inhibitory effects of TLD treatment on Eca109 proliferation.

Wilfoside C3N Promotes Tumor Cell Death by Activating Gammadelta T Cells-Mediated Anti-tumor Immunity

Vδ1^+γδ T lymphocytes are known to play important roles in anti-tumor immunity.We recently reported an anti-tumor activity of wilfoside C3 N,an active component extracted from Chinese medicinal herbs.In the current study,we evaluated the role of Vδ1^+γδ T cells in C3 N anti-tumor activity using an in vitro cell co-culture model.We found that C3 N induced the ECA109 tumor cells to undergo apoptosis in the presence of Vδ1^+γδ T cells.The level of ECA109 apoptosis maximized when both C3 N and Vδ1 + γδ T cells were present,which correlated with the increased expression of Fas on ECA109 and Fas ligand on Vδ1^+γδ T cells induced by C3 N.In addition,C3 N also enhanced secretion of cytokines,perforin and granzymes by Vδ1^+γδ T cells.These observations suggest that activation of Vδ1^+ γδ T cells may play a critical role in C3N-mediated anti-tumor activity.

EXPRESSION OF PLACENTAL ALKALINE PHOSPHATASE IN ESOPHAGEAL CANCER CELL LINE Eca109

The expression and properties of alkaline phosphatase (ALP) in Eca109 cells, a cell line derived fromhuman esophageal cancer were studied with specific inhibition assay and polyacrylamide gel electrophoresis.The results showed that ALP of Eca109 cells was heat stable and was strongly inhibited by L-pheuylalanine, but slightly inhibited by urea. Preduisolone could causedramatic increase in activity of ALP, but no change in ALP isozyme and concomitant increase in lactic dehydrogenase activity were found after prednisolone treatment. The results suggested that placental alkaline phosphatase as an oncodevelopmental gene product could be expressed ectopically by Eca109 cells and prednisolone could specifically induce increase in its activity.