PURPOSE: Sorafenib, a multikinase inhibitor, is the standard therapy for patients with advanced-stage hepatocellular carcinoma (HCC). However, resistance develops to the treatment, therefore, we tried to unravel the underlying mechanism in the resistance of HCC cells to sorafenib via the development of more effective therapeutic strategies. MATERIALS AND METHODS: Various liver cancer cell lines were treated with either sorafenib only or with sorafenib after infection of adenovirus expressing short hairpin RNA (shRNA) against transforming growth factor-β (TGF-β) and p38 activity was examined using western blotting. RESULTS: p38 MAP kinase activity was inhibited by low concentrations of sorafenib, which could potentially lead to sorafenib resistance in HCC cell lines. Subsequently, we used constitutive form of MKK3/6 (MKK3/6E) to confirm that massive cell death was induced by the activation of p38, and demonstrated the ability to activate p38 without any stimulation. In addition, sorafenib resistance was reduced by the activation of p38. Subsequently, we confirmed that TGF-β shRNA effectively recovered the phosphorylation of p38 inhibited by sorafenib, and increased the sensitivity of HCC cells to sorafenib, thereby inducing cell death and overcoming the resistance of HCC cells to sorafenib. CONCLUSION: Our study provides a new therapeutic strategy for HCC that overcomes the resistance of HCC to sorafenib by down-regulation of TGF-β.
Adenoviridae ; Blotting, Western ; Carcinoma, Hepatocellular* ; Cell Death ; Cell Line ; Down-Regulation* ; Humans ; Liver Neoplasms ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; RNA, Small Interfering

The objective of this study was to assess dietary habits and nutrition knowledge of elementary school students who use community food-service centers according to family type. The subjects were comprised of 147 individuals in low-income households, aged from 7 to 12 years, and who consumed free meals at community welfare centers or at local children's centers in Seoul and Kyunggi-do, Korea. Dietary habits and dietary intake were obtained using 24-hr recall. Children in low-income single parent families skipped breakfast more frequently than children in low-income married parent families. No difference in nutrition intake or dietary habits was observed between children in low-income single parent families and children in low-income married parent families. More interest and financial support of the government are required to develop nutrition education and food assistance programs for children in low-income single parent families.
Aged ; Breakfast ; Child ; Family Characteristics ; Financial Support ; Food Assistance ; Food Habits ; Food Services ; Humans ; Korea ; Meals ; Nutritional Status ; Parents ; Single-Parent Family