P38 Signal Transduction Pathway Has More Cofactors on Apoptosis of SGC-7901 Gastric Cancer Cells Induced by Combination of Rutin and Oxaliplatin.

Qi Li,Meng Qin,Qi Tan,Yang Zhang,Zehui Gu,Suxian Chen,Liqun Ren,Tong Zhang

doi:10.1155/2019/6407210

Abstract

Currently, gastric cancer treatment is mainly based on first-line intervention with oxaliplatin (OXA) after surgical resection, but the application of OXA has been limited due to the toxic side effects caused by the cumulative dose. The toxicity of OXA mainly includes hepatotoxicity, nephrotoxicity, and ototoxicity, and there is an urgent clinical need to find alternatives that are less toxic and more effective. Rutin (RT) is a natural flavonoid with many biological activities. Studies have found that RT inhibits tumor cell growth and enhances their sensitivity toward certain drugs. As the underlying impact of RT on gastric cancer and its molecular mechanism remain poorly understood, we performed a series of experiments to determine whether RT has the effect of treating gastric cancer, and whether it can cooperate with OXA to treat gastric cancer and its related mechanisms. In the present study, we founded that RT suppressed cell viability, inhibited cell proliferation by causing G0/G1 arrest, and induced apoptosis in SGC 7901 cells. And RT can play as an antitumor agent together with OXA. The mechanism of RT-induced apoptosis may be associated with the activation of the p38/Caspase signal pathway. These results demonstrated the potential of RT as a promising therapeutic compound to treat gastric cancer. At the same time, RT can synergize with OXA to reduce the dose of OXA and reduce the toxicity.

Highlights

Gastric cancer, one of the most common malignant tumors worldwide, is caused by the gastric mucosal epithelium, severely affects patients’ health and quality of life. ere are obvious regional differences in its occurrence, with Japan, Korea, and China being high-risk areas in Asia
Cell Line. e human normal gastric mucosal epithelial cell lines NGEC was acquired from the College of Basic Medicine of Jilin University, human gastric cancer cell lines SGC-7901 was acquired from the laboratory of the College of Life Sciences of Jilin University and frozen before use
Effect of Different Drugs on the Toxicity of NGEC Cells and the Viability of SGC-7901 Cells. e results of the MTT assay showed that the viability of SGC-7901 cells treated with different concentrations of DOX and RT for 24 h was significantly inhibited compared with control group (Figures 1(a) and 1(b)), and the combined effect of the two drugs was stronger than their individual effects, while the addition of p38 inhibitor reduced the inhibitory effect of RT and OXA on cell proliferation (Figure 1(c))

Summary

Introduction

One of the most common malignant tumors worldwide, is caused by the gastric mucosal epithelium, severely affects patients’ health and quality of life. ere are obvious regional differences in its occurrence, with Japan, Korea, and China being high-risk areas in Asia. One of the most common malignant tumors worldwide, is caused by the gastric mucosal epithelium, severely affects patients’ health and quality of life. Gastric cancer is one of the most prominent malignant tumors in China. It accounts for the fifth highest incidence rate and third highest mortality rate worldwide, causing heavy medical burdens [1]. P38 mitogen-activated protein kinase (MAPK) is the most important member of the MAPK family. It is involved in cell survival, differentiation, apoptosis, and cell cycle regulation. It has been found to be abnormally activated in a variety of tumors, including gastric cancer tissues [3, 4]

Methods

Results

Conclusion