Background Esophageal cancer causes considerable mortality and is ranked as the 6 th most prevalent type of cancer across the world. At present, there is no effective esophageal cancer chemotherapy without adverse effects. Moreover, emergence of drug resistance among cancer is another obstacle in the treatment of esophageal cancer. Novel molecules of plant origin may prove beneficial in the development of chemotherapy for esophageal carcinoma. In this study we examined the anticancer effects of phillygenin against the vindesine-resistant esophageal cancer cell line SH-1-V1. Material/Methods The proliferation rate of SH-1-V1 cells was determined by WST-1 assay. Apoptosis was confirmed by propidium iodide (PI) staining. Cell cycle analysis, ROS, and MMP determination were performed by flow cytometery. Protein expression was assessed by Western blot analysis. Results We found that phillygenin inhibited the growth of SH-1-V1 cells and exhibited an IC 50 of 6 μM. Investigation of the underlying mechanism revealed that phillygenin triggered apoptotic cell death of the SH-1-V1 cells, which was also associated with enhancement of Bax expression and decreased expression of Bcl-2. Moreover, the expression of cleaved caspase 3 and 9 also increased upon phillygenin treatment. Phillygenin also caused a significant increase in ROS production, concomitant with decreased MMP levels. Phillygenin also caused arrest of cells in the G2/M phase of the cell cycle. In vivo evaluation of phillygenin revealed that it can inhibit tumor weight and volume, suggesting the anticancer potential of phillygenin. Conclusions In brief, phillygenin inhibited in vitro and in vivo cancer cell growth in drug-resistant human esophageal cancer cells, and these effects were mediated via apoptosis, ROS generation, mitochondrial membrane potential loss, and activation of the NF-κB signalling pathway.

Non-small cell lung cancer, as the most frequent type lung cancer, has lower survival rate of 5 years, despite improvements in surgery and chemotherapy. Previous studies showed immature colon carcinoma transcript 1 is closely related to tumorigenesis of human cancer cells. In the present study, we found immature colon carcinoma transcript 1 was overexpressed in lung cancer tissues using Oncomine database mining, and the biological effect of immature colon carcinoma transcript 1 was investigated in non-small cell lung cancer cell lines 95D and A549. Lentivirus-mediated RNA interference was used to knock down immature colon carcinoma transcript 1 expression in 95D and A549 cells in vitro, and the knockdown efficiency was determined using quantitative real-time polymerase chain reaction and Western blot assay. Knockdown of immature colon carcinoma transcript 1 significantly suppressed non-small cell lung cancer cell proliferation and colony formation ability confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay. Flow cytometry was applied to measure cell cycle arrest, and the result showed the cell cycle arrested in G/M phase in 95D cells and arrested in G/G phase in A549 cells. Furthermore, we measured the levels of cell cycle-associated proteins by Western blot analysis and found immature colon carcinoma transcript 1 -mediated cell proliferation inhibition appeared due to downregulation of cell cycle activator cyclin D1 and upregulation of cell cycle inhibitor p21. In addition, immature colon carcinoma transcript 1 silencing significantly induced non-small cell lung cancer cell apoptosis by annexin V/7-amino-actinomycin D double-staining assay. All our data suggest that immature colon carcinoma transcript 1 may play an important role for non-small cell lung cancer cell proliferation and could be a potential molecular target for diagnosing and treating human non-small cell lung cancer.

Radiotherapy is a major therapeutic approach in non-small cell lung cancer but is restricted by radioresistance. Although Akt signaling promotes radioresistance in non-small cell lung cancer, it is not well understood how Akt signaling is activated. Since intracellular calcium (Ca) could activate Akt in A549 cells, we investigated the relationship between intracellular calcium (Ca) and Akt signaling in radioresistant A549 cells by establishing radioresistant non-small cell lung cancer A549 cells. The radioresistant cell line A549 was generated by dose-gradient irradiation of the parental A549 cells. The cell viability, proliferation, and apoptosis were, respectively, assessed using the cell counting kit-8, EdU labeling, and flow cytometry analysis. The phosphorylation of Akt was evaluated by Western blotting, and the intracellular Ca concentration was assessed by Fluo 4-AM. The radioresistant A549 cells displayed mesenchymal morphology. After additional irradiation, the radioresistant A549 cells showed decreased cell viability and proliferation but increased apoptosis. Moreover, the intracellular Ca concentration and the phosphorylation level on the Akt473 site in radioresistant A549 cells were higher than those in original cells, whereas the percentage of apoptosis in radioresistant A549 cells was less. All these results could be reversed by verapamil. In conclusion, our study found that intracellular Ca could promote radioresistance of non-small cell lung cancer cells through phosphorylating of Akt on the 473 site, which contributes to a better understanding on the non-small cell lung cancer radioresistance, and may provide a new target for radioresistance management.

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