periplocin and Stomach-Neoplasms

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor family, induces apoptosis in a variety of cancer cells. However, gastric cancer (GC) cells are insensitive to TRAIL usually. In the previous study, we showed that Periplocin could induce apoptosis in GC cells via the activation of ERK1/2-EGR1 pathway. In the present study, we have shown that the combination of Periplocin and TRAIL had a greater inhibitory effect on gastric cancer cell viability in vitro and in vivo than Periplocin or TRAIL alone. Through upregulating the expression of DR4 and DR5 at transcriptional and protein levels, Periplocin enhanced the sensitivity of gastric cancer cells to TRAIL. Furthermore, enhanced activity of ERK1/2-EGR1 pathway was responsible for upregulating of DR4 and DR5 uponPeriplocin treatment, subsequently reducing the expression of Mcl-1 and Bcl2 and activating Bid and caspase-3/8. Collectively, these data implied that Periplocin might act as a sensitizer of TRAIL and could be a potential strategy for the treatment of GC.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Resistance, Neoplasm; Drug Synergism; Gene Expression Regulation, Neoplastic; Humans; Male; MAP Kinase Signaling System; Mice; Receptors, TNF-Related Apoptosis-Inducing Ligand; Saponins; Stomach Neoplasms; TNF-Related Apoptosis-Inducing Ligand; Up-Regulation; Xenograft Model Antitumor Assays

Periplocin is extracted from the traditional herbal medicine cortex periplocae, which has been reported to suppress the growth of cancer cells. However, little is known about its effect on gastric cancer cells.. Gastric cancer cells were treated with periplocin, and cell viability was assessed using MTS assay. Flow cytometry and TUNEL staining were performed to evaluate apoptosis, and protein expression was examined by western blotting. Microarray analysis was used to screen for changes in related genes.. We found that periplocin had an inhibitory effect on gastric cancer cell viability in a dose-dependent manner. Periplocin inhibited cell viability via the ERK1/2-EGR1 pathway to induce apoptosis. Periplocin also inhibited the growth of tumor xenografts and induced apoptosis in vivo.. Our results show that periplocin inhibits the proliferation of gastric cancer cells and induces apoptosis in vitro and in vivo, indicating its potential to be used as an antitumor drug.

Topics: Animals; Apocynaceae; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Early Growth Response Protein 1; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Plant Extracts; Saponins; Signal Transduction; Stomach Neoplasms; Transplantation, Heterologous