ABSTRACT
Bovine lactoferrin (bLF) is a multifunctional protein with anti-inflammatory, antibacterial, antiviral, anti-tumour and immunoregulatory effects. The present study was conducted to evaluate the anti-inflammatory and anti-tumour effects of liposomal bLF (LbLF) in a 1,2-dimethylhydrazine (DMH)/dextran sulphate sodium (DSS)-induced model of carcinogenesis in F344 rats. F344 rats were randomly divided into three groups: Control (water), 500 or 1,000 mg/kg/day LbLF; additionally, the rats were injected with DMH (20 mg/kg) once per week for 8 consecutive weeks, after one week of drinking water containing 1% DSS. All rats were sacrificed at 25 weeks. The tissues were examined for the presence of aberrant crypt foci (ACF) and subjected to histopathological analysis. Additionally, human colon cancer cells were utilised to investigate the effect of LbLF on proliferation and inflammation. Rats from the 500 and 1,000 mg/kg/day LbLF groups harboured significantly fewer colon ACF, adenomas and adenocarcinomas than the rats from the control group. Lastly, it was demonstrated that LbLF inhibits cell growth and TNF-α mRNA expression. These data support the hypothesis that LbLF affects colorectal carcinogenesis by suppressing inflammation and cell proliferation in rats.
ABSTRACT
Poly (ADP-ribose) polymerases (PARPs) are enzymes that transfer ADP-ribose groups to target proteins and are involved in a variety of biological processes. PARP6 is a novel member, and our previous findings suggest that PARP6 may act as a tumor suppressor via suppressing cell cycle progression. However, it is still unclear that PARP6 function besides growth suppression in colorectal cancer (CRC). In this study, we examined tumor suppressive roles of PAPR6 in CRC cells both in vitro and in vivo. We found that PARP6 inhibited colony formation, invasion and migration as well as cell proliferation. Moreover, ectopic overexpression of PARP6 decreased Survivin expression, which acts as an oncogene and is involved in apoptosis and mitosis. We confirmed the inverse correlation between PARP6 and Survivin expression in CRC cases by immunohistochemistry. Importantly, CRC cases with downregulation of PARP6 and upregulation of Survivin showed poor prognosis. In summary, PARP6 acts as a tumor suppressor via downregulating Survivin expression in CRC. PARP6 can be a novel diagnostic and therapeutic target together with Survivin for CRC.
Subject(s)
ADP Ribose Transferases/genetics , Colorectal Neoplasms/genetics , Inhibitor of Apoptosis Proteins/metabolism , Cell Proliferation , Colorectal Neoplasms/pathology , Down-Regulation , Female , Genes, Tumor Suppressor , Humans , Male , Signal Transduction , SurvivinABSTRACT
OBJECTIVE: Long-term exposure study was conducted to investigate the effects of extremely low-frequency electromagnetic field on the tumor promotion process and fertility. METHODS: Ten pregnant C57BL/6NCrj mice were exposed to 50 Hz field 500 mG for 1 week (12 h per day), and 24 male and 42 female B6C3F1mice born from them were further exposed up to 15.5 months. As a control group, 10 pregnant mice were bred without exposure, and 30 produced male and 32 female mice were observed without exposure for the same period. RESULTS: Mean body weights of exposed groups of male and female mice were decreased significantly than those of the control groups. In exposed mice, there was no increased incidence of liver and lung tumor. In female mice, the incidence of chronic myeloid leukemia [3/42 (7%)] in the exposed group was significantly greater than in the control group. The size of seminiferous tubules in the EMF exposed groups were significantly less than the control group. CONCLUSIONS: These data support the hypothesis that long-term exposure of 50 Hz magnetic fields is a significant risk factor for neoplastic development and fertility in mice.
