The ROS derived mitochondrial respirstion not from NADPH oxidase plays key role in Celastrol against angiotensin II-mediated HepG2 cell proliferation.

Angiotensin II (AngII) is an important factor that promotes the proliferation of cancer cells, whereas celastrol exhibits a significant antitumor activity in various cancer models. Whether celastrol can effectively suppress AngII mediated cell proliferation remains unknown. In this study, we studied the effect of celastrol on AngII-induced HepG2 cell proliferation and evaluated its underlying mechanism. The results revealed that AngII was able to significantly promote HepG2 cell proliferation via up-regulating AngII type 1 (AT1) receptor expression, improving mitochondrial respiratory function, enhancing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, increasing the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines. The excess ROS from mitochondrial dysfunction is able to cause the apoptosis of tumor cells via activating caspase3 signal pathway. In addition, the reaction between NO and ROS results in the formation of peroxynitrite (ONOO-), and then promoting cell damage. celastrol dramatically enhanced ROS generation, thereby causing cell apoptosis through inhibiting mitochodrial respiratory function and boosting the expression levels of AngII type 2 (AT2) receptor without influencing NADPH oxidase activity. PD123319 as a special inhibitor of AT2R was able to effectively decreased the levels of inflammatory cytokines and endothelial nitric oxide synthase (eNOS) activity, but only partially attenuate the effect of celastrol on AnII mediated HepG2 cell proliferation. Thus, celastrol has the potential for use in liver cancer therapy. ROS derived from mitochondrial is an important factor for celastrol to suppress HepG2 cell proliferation.

Nuclear and cytoplasmic Id-1 expression patterns play different roles in angiogenesis and lymphangiogenesis in gastric carcinoma.

The purpose of the study was to investigate the expression and impact of Id-1 (inhibitor of differentiation) on tumor progression, angiogenesis, and lymphangiogenesis in gastric adenocarcinoma. The study included 97 cases of gastric adenocarcinoma, which were surgically excised at the Second Hospital of Shandong University. Immunohistochemistry was used to detect the Id-1 expression, and dual-labeling immunohistochemistry was used to evaluate the microvessel density (MVD) and lymphatic vessel density (LVD). The Id-1 protein was mainly expressed with nuclear staining in well-differentiated carcinoma, but with cytoplasmic staining in moderately and poorly differentiated carcinoma, which showed a significant difference (P < .0001). Moreover, the expression patterns had different and crucial effects on angiogenesis and lymphangiogenesis. Nuclear staining of Id-1 inhibited angiogenesis, but cytoplasmic staining promoted angiogenesis (MVD, 110.57 ± 32.32 vs 141.45 ± 55.60) (P < .05). Consistent with their roles in angiogenesis, the nuclear and cytoplasmic expressions of Id-1 had similar effects on lymphangiogenesis: nuclear expression inhibited and cytoplasmic expression promoted lymphangiogenesis (LVD, 2.62 ± 1.03 vs 4.05 ± 2.04) (P < .05). Microvessel density and LVD showed no significant difference in low-and high-Id-1 expression groups (P > .05). Aberrant expression of Id-1 from nuclear to cytoplasm is accompanied with tumor malignant progression, which promotes angiogenesis and lymphangiogenesis; and Id-1 should be developed as a target for gastric carcinoma therapy.

[Screening study of the kinetogenic effects of serum containing four Chinese materia medicas on the colonic smooth muscle cells in rats].

OBJECTIVE: To study the kinetogenic effects of serum containing Semen Arecae, Dandelion, Semen raphani and Atractylodes macrocephala on the colonic smooth muscle cells of rats. METHODS: Serum containing Chinese materia medicas was made according to standard methods. Smooth muscle cells were isolated from the muscle layers of Wistar rat's colon, referred to modified Bitar's method. The contractile response of colonic smooth muscle cells to serum containing Chinese materia medicas (10%, 50%, 100% concentration) and other medicines (blank and 1 x 10(-3) mol/L acetylcholine) were separately observed. The contractility was presented by the decrease of the cell length between the drug groups and the control. RESULTS: Serum containing each Chinese materia medica can make dose-dependent contraction at different concentrations (P < 0.05), but the strongest effect of each serum had no significant difference (P > 0.05). CONCLUSION: Serum containing Semen Arecae, Dandelion, Semen raphani and Atractylodes macrocephala can make notable contraction on colonic smooth muscle cells in rats.