BackgroundThe National Comprehensive Cancer Network (NCCN) guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because gastric cancer demonstrates limited sensitivity to radiotherapy, a radiosensitizer might therefore be useful to enhance the radiosensitivity of patients with advanced gastric carcinoma. In this study, we evaluated if propranolol, a β-adrenoceptor (β-AR) antagonist, could enhance radiosensitivity and explored its precise molecular mechanism in gastric cancer cells.MethodsHuman gastric adenocarcinoma cell lines (SGC-7901 and BGC-823) were treated with or without propranolol and exposed to radiation. Cell viability and clonogenic survival assays were performed, and cell apoptosis was evaluated with flow cytometry. In addition, the expression of nuclear factor κB (NF-κB), vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), and epidermal growth factor receptor (EGFR) were detected by western blot and real-time reverse transcription polymerase chain reaction (PCR).ResultsPropranolol combined with radiation decreased cell viability and clonogenic survivability. Furthermore, it also induced apoptosis in both cell lines tested, as determined by Annexin V staining. In addition, treatment with propranolol decreased the level of NF-κB and, subsequently, down-regulated VEGF, COX-2, and EGFR expression.ConclusionsTaken together, these results suggested that propranolol enhanced the sensitivity of gastric cancer cells to radiation through the inhibition of β-ARs and the downstream NF-κB-VEGF/EGFR/COX-2 pathway.

Abstract. Nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in the NAD + salvage pathway, is overexpressed and important in the carcinogenesis in several types of cancers. The expression of Nampt and its role in gastric cancer remain largely unknown. In this study, using real-time PCR and Western blotting we found that Nampt was overexpressed at the mRNA and protein levels, respectively, in established gastric cancer cells and human gastric cancer tissues. The specific Nampt inhibitor FK866 repressed gastric cancer cell proliferation, as assessed by MTT assay. Using transwell and soft agar clonogenic assays, we also found that FK866 suppressed gastric cancer cell migration and anchorageindependent growth, respectively. These inhibitory effects of FK866 were accompanied by significantly decreased expression of VEGF, MMP2, MMP9 and NF-κB. As determined by MTT assay and flow cytometry, FK866 also increased the chemosensitivity of gastric cancer cells to fluorouracil by greater inhibition of cell proliferation and the induction of apoptosis. Our findings indicate that Nampt may be a new therapeutic target for gastric cancer. IntroductionGastric cancer is the fourth most common malignancy in the world and causes ~800,000 deaths annually worldwide (1). For patients with recurrent, metastatic, or advanced gastric cancer, fluorouracil (5-FU) is a commonly used chemotherapeutic drug (2). However, the toxic side effects associated with 5-FU remain a significant challenge to its use. The development of more effective therapeutic drugs with minimal side effects is crucial, and is dependent on a better understanding of the molecular mechanism underlying gastric carcinogenesis.Nicotinamide adenine dinucleotide (NAD) is an essential cofactor found in all cells and plays key roles as a carrier of electrons during redox reactions. The rate-limiting enzyme involved in the biosynthesis of NAD from the nicotinamide precursor is nicotinamide phosphoribosyltransferase (Nampt) (3). Increasing evidence demonstrates that Nampt is a multifunctional enzyme and is important in metabolism and immune response as well as cancer (4). Nampt is also known as pre-B-cell colony enhancing factor (PBEF1), a presumptive cytokine (5), and as visfatin, an insulin-mimetic adipocytokine secreted by visceral fat (6) that is also encoded by the PBEF1 gene (5).Cross-talk between the two NAD-dependent enzymes SIRT1 (also known as sirtuin 1 or NAD-dependent deacetylase sirtuins-1) deacetylase and poly(ADP-ribose) polymerase 1 (PARP1) plays a major role in cell viability under stress (7). By binding to and thereby causing the deacetylation of PARP1, SIRT1 protects cells from PARP1-mediated cell death. SIRT1 has also been shown to control PARP1 at the transcriptional level by negatively regulating the PARP1 gene promoter. The activity of SIRT1 can be positively regulated by Nampt, making Nampt a player in promoting cell survival under stress (8).Nampt was first reported to be overexpressed in colorectal cancer (9,10). It is also overexpressed i...

No abstract

Dietary anthocyanin compounds have multiple biological effects, including antioxidant, anti-inflammatory, and anti-atherosclerotic characteristics. The present study evaluated the anti-tumor capacity of mulberry anthocyanins (MA) in thyroid cancer cells. Our data showed that MA suppressed SW1736 and HTh-7 cell proliferation in a time- and dose-dependent manner. Meanwhile, flow cytometry results indicated that MA significantly increased SW1736 and HTh-7 cell apoptosis. We additionally observed that SW1736 and HTh-7 cell autophagy was markedly enhanced after MA treatment. Importantly, anthocyanin-induced cell death was largely abolished by 3-methyladenine (3-MA) or chloroquine diphosphate salt (CQ) treatment, suggesting that MA-induced SW1736 and HTh-7 cell death was partially dependent on autophagy. In addition, activation of protein kinase B (Akt), mammalian target of rapamycin (mTOR), and ribosomal protein S6 (S6) were significantly suppressed by anthocyanin exposure. In summary, MA may serve as an adjunctive therapy for thyroid cancer patients through induction of apoptosis and autophagy-dependent cell death.

We studied the clinical effects of percutaneous radiofrequency ablation (RFCA) combined with trans-catheter arterial chemoembolization (TACE) in the treatment of breast cancer with liver metastasis. Eighty-eight patients with a diagnosis of breast cancer with liver metastasis for the first time and patients with liver metastasis after radical mastectomy were consecutively selected. The subjects were divided according to the different treatment methods. They were divided either into the control group of 50 cases or the observation group of 38 cases. Breast cancer patients underwent radical mastectomy with conventional systemic venous chemotherapy. The liver metastasis control group used TACE, while the observation group combined RFCA with TACE. The two groups were followed up for a median time of 20 months, and the clinical effects were compared. The effective rate of the observation group was higher than that of the control group; differences were statistically significant (P<0.05). There was no differences in the incidence of complications between the two groups (P>0.05). The progression free survival, median survival time and survival rate of the observation group were increased; differences were statistically significant (P<0.05). Therefore, RFCA combined with TACE in the treatment of breast cancer with liver metastasis is safe and effective.