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Researches regarding mitogen-inducible gene 6 (Mig-6) have confirmed its role as a tumor suppressor and progesterone resistance factor in endometrium. In this study, after confirming the downregulation of Mig-6 protein in endometrial carcinoma (EC) tissues, the expression of Mig-6 was upregulated in Ishikawa cells by pCMV6-Mig-6 plasmid. We observed the increased apoptosis, decreased proliferation and invasion potential of Ishikawa cells after upregulation of Mig-6. The proapoptosis ability of P4 significantly enhanced by 39.36%, the antiproliferation ability increased by 37.90% and the anti-invasion ability increased by 48.89%, suggesting the antiprogesterone resistance potential of Mig-6 in endometrium. In addition, the results suggested that Mig-6 may induce Ishikawa cell apoptosis through the mitochondrial pathway, inhibit cell proliferation via the extracellular signal-regulated kinase pathway and the anti-invasion potential may associate with matrix metalloproteinase (MMP)-2 and MMP-9 downexpression. Therefore, upregulation of Mig-6 may add a new strategy to suppress endometrial tumorigenesis and attenuate the progesterone resistance during P4 treatment. [ABSTRACT FROM AUTHOR]

Malignant ascites is common in various types of cancers and is difficult to manage. Vascular endothelial growth factor (VEGF) has a pivotal role in malignant ascites. The matrix protein of vesicular stomatitis virus (VSVMP) has been shown to inhibit host gene expression and induce the apoptosis of cancer cells. The present study was designed to determine whether VSVMP suppresses the formation of ascites in ascites-producing peritoneal carcinomatosis. BALB/c female mice, 6-8 weeks old, bearing peritoneal tumors of H22 or MethA cells received an intraperitoneal administration of 50 μg VSVMP/250 μg liposome complexes, 50 μg empty plasmid/250 μg liposome complexes or 0.9% NaCl solution, respectively, every 2 days for 3 weeks. Administration of VSVMP resulted in a significant inhibition in ascites formation, improvement in health condition and prolonged survival of the treated mice. Decreased peritoneum osmolarity and reduced tumor vascularity coincided with dramatic reductions in the VEGF level in ascites fluid and plasma. Examination of floating tumor cells collected from the peritoneal wash revealed an apparently increased number of apoptotic cells and profound downregulation of VEGF mRNA in the VSVMP-treated mice. Our data indicate for the first time that in BALB/c mice bearing H22 or MethA cell peritoneal tumors, VSVMP may inhibit VEGF production and suppress angiogenesis, consequently abolishing ascites formation. [ABSTRACT FROM AUTHOR]

Gene therapy promises to become an alternative choice for the treatment of hepatic cancer. In many cancers, the delivery of chimeric proteins by adenovirus vector has been reported to induce apoptosis. This study was performed to evaluate whether the recombinant adenovirus interleukin (IL)-24-Bax can induce apoptosis in hepatocellular carcinoma cells in vitro and in vivo. Several recombinant adenoviruses were constructed, and the expression of their encoded proteins was measured. The effects of the recombinant adenovirus on hepatocellular carcinoma cells and the normal hepatocyte cell line were investigated through cell viability and apoptosis assays after the cells were treated with Ad.Luc, Ad.IL-24, Ad.Bax or Ad.IL-24-Bax. The mechanism involved was also explored. A tumor-bearing mouse model was used to evaluate the effects of the adenovirus on tumor volume and cell apoptosis in vivo. Ad.IL-24-Bax selectively suppressed growth of hepatocellular carcinoma cells and induced apoptosis, but it had little influence on the normal hepatocytes. The mechanism of this response may include the effect of the 10HRE/VEGF385 promoter and the synergistic effect of IL-24 and Bax. Ad.IL-24-Bax also suppressed tumor growth in nude mice and induced apoptosis. Ad.IL-24-Bax may be a useful tool for gene therapy of hepatic cancer. [ABSTRACT FROM AUTHOR]