Reversal of Multidrug Resistance by the Chinese Medicine Yiqi Jianpi Huaji Decoction and the Mechanism of Action in Human Gastric Cancer SGC7901/VCR Cells.

Wei-Bing Li,Chen Yu,Yong-Ming He,Yang Li

doi:10.1155/2015/390812

Abstract

Yiqi Jianpi Huaji Decoction (YJHD), a traditional Chinese medicinal formula composed of twelve ingredients, has recently been reported to have a good clinical curative effect. The purpose of the present study was to evaluate the effects of YJHD on SGC7901/VCR gastric cancer cells and to elucidate the possible mechanism of action. First, the effects of a low dose of YJHD in combination with chemotherapeutic agents on SGC7901/VCR cells were assessed using the CCK-8 assay and flow cytometry, and the effects of YJHD on genes and proteins involved in drug resistance (MDR1, MRP, TUBB3, STMN1, and TS) were evaluated. Furthermore, transfection of SGC7901/VCR cells with siRNAs targeting these genes inhibited their expression, and the efficacy of vincristine against the cells was dramatically improved in vitro when these genes were silenced. These results demonstrate that low-dose YJHD inhibited cell proliferation, induced apoptosis, reversed MDR, and increased sensitivity to chemotherapeutic agents in vitro by downregulating P-gp, MRP, TUBB3, and STMN1 expression. MDR can be reversed by siRNAs targeting genes involved in MDR, and this strategy for cancer treatment should be evaluated in future studies.

Highlights

Stomach cancer was the cause of 738,000 deaths in 2008, corresponding to approximately 9.7% of the total number of cancer-related deaths [1], and the incidence and mortality rates for stomach cancer are significantly higher in China than in the rest of the world [2]
The major factors responsible for the increased mortality and morbidity associated with gastric cancer are the progression of the disease and failure of chemotherapy caused by multidrug resistance (MDR) [3] via the overexpression of the MDR1 and MRP genes [4]
SGC7901/Vincristine sulfate (VCR) and SGC7901 cells were treated with 0–6 mg/mL Yiqi Jianpi Huaji Decoction (YJHD), and the results demonstrate the dose- and time-dependent inhibition of proliferation by YJHD (Figure 1(a)), inducing a greater than 90% reduction in the number of cells at the highest concentration (6 mg/mL)

Summary

Introduction

Stomach cancer was the cause of 738,000 deaths in 2008, corresponding to approximately 9.7% of the total number of cancer-related deaths [1], and the incidence and mortality rates for stomach cancer are significantly higher in China than in the rest of the world [2]. The major factors responsible for the increased mortality and morbidity associated with gastric cancer are the progression of the disease and failure of chemotherapy caused by multidrug resistance (MDR) [3] via the overexpression of the MDR1 and MRP genes [4]. Several other mechanisms are involved in the development of MDR in tumor cells, including alterations in drug targets (e.g., TUBB3, STMN1, and TS), the activation of detoxifying systems, the interruption of signaling pathways, and alterations in regulators involved in cell cycle control [6], and the above genes exhibit chemotherapy-related effects. Several studies using drugs that target microtubules have found that β-tubulin III (TUBB3) and stathmin 1 (STMN1) are directly related to the efficacy of chemotherapy [6]. Elevated TUBB3 expression is related to vincristine resistance and a short

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