SUZ12 RNA Interference Inhibits the Invasion of Gastric Carcinoma Cells.

In order to observe the regulation effects of SUZ12 gene to the invasion of gastric carcinoma cells and the mechanisms, the expressions of SUZ12 protein in 86 patients with different infiltrating degree (Tis-T4), lymph node metastasis (N0-N3) and far metastasis (M0-M1) were detected by immunohistochemical staining. The siRNA to SUZ12 was designed and synthesized and transfected into MKN28 cells. The effects of SUZ12 siRNA to cell invasion were detected by soft agar colony forming test and Transwell cabin model. The related protein was detected by Western-Blot. We found the expression of SUZ12 in gastric carcinoma tissues (23.58 ± 9.89%) was obviously higher than that in para-cancer tissue (1.12% ± 0.12%) (p < 0.01). The expression of SUZ12 was related to the infiltrating degree, and demonstrated an increasing tendency from Tis-T4, or from N0-N3. The expression of SUZ12 in M0 was obviously lower than in M1, p < 0.01. The level of SUZ12 was descent obviously after transfected SUZ12 siRNA (p < 0.01). The number of cell clone was reduced in dose dependent of siRNA and the cells permeated through filter membrane were decreased after transfected siRNA. Inhibition of SUZ12 caused an obviously descent of VEGF, MMP-2 and MMP-9 (0.22 ± 0.06, 0.12 ± 0.03, 0.08 ± 0.02) compared to non transfected group (0.87 ± 0.08, 0.92 ± 0.16, 1.05 ± 0.18) respectively (p < 0.01). We draw the conclusion that the expression of SUZ12 is increasing along with the degree of infiltrating and metastasis of gastric carcinoma. SUZ12 siRNA inhibits the invasion of gastric carcinoma cells and the expression of VEGF, MMP-2 and MMP-9.

SUZ12 RNA interference inhibits the invasion of gastric carcinoma cells.

In order to observe the regulation effects of SUZ12 gene to the invasion of gastric carcinoma cells and the mechanisms, the expressions of SUZ12 protein in 86 patients with different infiltrating degree (Tis-T4), lymph node metastasis (N0-N3) and far metastasis (M0-M1) were detected by immunohistochemical staining. The siRNA to SUZ12 was designed and synthesized and transfected into MKN28 cells. The effects of SUZ12 siRNA to cell invasion were detected by soft agar colony forming test and Transwell cabin model. The related protein was detected by Western-Blot. We found the expression of SUZ12 in gastric carcinoma tissues (23.58±9.89%) was obviously higher than that in para-cancer tissue (1.12%±0.12%) (p<0.01). The expression of SUZ12 was related to the infiltrating degree, and demonstrated an increasing tendency from Tis-T4, or from N0-N3. The expression of SUZ12 in M0 was obviously lower than in M1, p<0.01. The level of SUZ12 was descent obviously after transfected SUZ12 siRNA (p<0.01). The number of cell clone was reduced in dose dependent of siRNA and the cells permeated through filter membrane were decreased after transfected siRNA. Inhibition of SUZ12 caused an obviously descent of VEGF, MMP-2 and MMP-9 (0.22±0.06, 0.12±0.03, 0.08±0.02) compared to non transfected group (0.87±0.08, 0.92±0.16, 1.05±0.18) respectively (p<0.01). We draw the conclusion that the expression of SUZ12 is increasing along with the degree of infiltrating and metastasis of gastric carcinoma. SUZ12 siRNA inhibits the invasion of gastric carcinoma cells and the expression of VEGF, MMP-2 and MMP-9.

The role of neural-related factors in the metastasis of the gastrointestinal cancer.

Neurotransmitters are identified to be endogenous chemicals and act on neurons to transmit signals to each other or to a target cell across synapse. They are involved in many brain functions including analgesia, reward, food intake, metabolism, reproduction, social behaviors, learning, and memory. Recently, sympathetic nerve fibers were detected in many solid tumors including gastrointestinal cancer, supporting the idea that neural system has effects on tumor progression. Neurotransmitters were secreted from the sympathetic nerve fibers and subsequently infiltrated into tumor tissues. Further studies disclosed the different mechanisms of various kinds of neurotransmitters in the progression of carcinogenesis, including tumor cell proliferation, angiogenesis, and tumor invasion and metastasis. Neurotransmitters are mainly subdivided into four types, amino acids, monoamines, peptides, and others, each of which contains multiple chemicals. For this reason, we cannot describe each in detail. In this review, we will focus on several important neurotransmitters including tachykinis, neuropeptide Y, and b-adrenergic receptors. How they function and their crosstalks with the immune system in the progression, especially the metastasis of gastrointestinal cancer, will be described. Finally, we will summarize the clinical implications in the treatment of gastrointestinal cancer.

siRNA targeting decoy receptor 3 enhances the sensitivity of gastric carcinoma cells to 5-fluorouracil.

In order to investigate the effects of RNA interference of decoy receptor 3 (DcR3) on the sensitivity of gastric cancer cells to 5-fluorouracil (5-FU) and the relevant mechanisms, siRNA against DcR3 was transfected into the gastric cancer cell line AGS. AGS cells were treated with different doses of 5-FU or for different time periods. The sensitivity of AGS cells to 5-FU was determined. The cell survival rate was detected by MTT assay. The apoptotic rate was determined by DAPI staining, and the expression of related proteins were detected by western blot analysis. The results showed that the cell survival rate was significanlty decreased in the knockdown group compared to the control group at different doses of 5-FU (P<0.01). After different time periods of treatment with 5-FU, the cell survival rate in the knockdown group was significantly decreased compared to the control group, respectively (P<0.01). The apoptotic rate of AGS cells in the knockdown group was increased along with the increasing dose of siRNA. The siRNA against DcR3 enhanced the expression of Fas, FasL, caspase-3 and caspase-8. In conclusion, knockdown of DcR3 by RNA interference enhances apoptosis and inhibits the growth of gastric cancer cells. Downregulation of DcR3 enhances the sensitivity of gastric cancer cells to 5-FU and increased the expression of Fas, FasL and caspase-3/8.

Inhibition of RhoA/ROCK signaling pathway promotes the apoptosis of gastric cancer cells.

BACKGROUND/AIMS: Ras homologue A (RhoA) plays a crucial role in the proliferation, apoptosis,adhesion and migration of gastric cancer cells. Rho associated kinase (ROCK) is an effector protein of RhoA. METHODOLOGY: In the present study, RhoA activity was inhibited by siRNA targeting RhoA andY-27632, an inhibitor of ROCK, and the role of RhoA/ROCK signaling pathway in the apoptosis of gastric cancer cells was investigated. RESULTS: RNAi of RhoA inhibited the survival and promoted the apoptotic of AGS cells. RhoA RNAi caused an obvious decrease of ROCK1 expression but an increase of caspase-3/cleaved-caspase-8. Inhibition of ROCK by Y-27632 inhibited the activity of RhoA and promoted the apoptosis. CONCLUSIONS: We speculate that RhoA/ROCK signaling pathway plays an important role in the regulation of apoptosis of gastric cancer, and to inhibit this pathway may promote the apoptosis of cancer cells. Thus, inhibition of RhoA/ROCK signaling pathway may become a novel target in the treatment of gastric cancer.