Bu-Zhong-Yi-Qi Decoction, the Water Extract of Chinese Traditional Herbal Medicine, Enhances Cisplatin Cytotoxicity in A549/DDP Cells through Induction of Apoptosis and Autophagy.

Ning Yu,Ying Xiong,Chun Wang

doi:10.1155/2017/3692797

Abstract

Cisplatin is one of the most active cytotoxic agents for non-small cell lung cancer (NSCLC) treatment. However, the development of cisplatin resistance is common. Bu-Zhong-Yi-Qi decoction (BZYQD), a Chinese traditional herbal medicine, is widely used for the enhancement of antitumor effect in other medications. In this study, we evaluated the effect and drug-resistance reversal mechanism of BZYQD combined with cisplatin on cisplatin-resistant A549/DDP cells. Our results showed that BZYQD exhibited direct cytotoxic and chemosensitizing effects. Cotreatment with BZYQD and cisplatin induced intrinsic apoptotic pathways which were measured by condensed nuclear chromatin, Annexin V/PI apoptosis assay, and apoptosis related proteins expression. In addition, cotreatment with BZYQD and cisplatin also activated autophagy, as indicated by an increase in LC3 puncta, classical autophagosomes and/or autolysosomes, and an accumulation of LC3-II and ATG7 protein. Finally, cotreatment with BZYQD and cisplatin resulted in the generation of ROS and scavenging ROS by NAC almost completely suppressing cell death. These results suggest that cotreatment with BZYQD and cisplatin might reverse cisplatin resistance by inducing ROS accumulation, which activates apoptosis and autophagy by oxidative stress. The combination of BZYQD and cisplatin may represent a novel approach in treatment for NSCLC and thus offer a new target for chemotherapy.

Highlights

Lung cancer is the most common cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 80∼85% of all lung cancers [1, 2]
To confirm the apoptosis induced by coincubation with Bu-ZhongYi-Qi decoction (BZYQD) and cisplatin, the percentage of apoptotic cells was measured by dual staining of cells with Annexin V and propidium iodide (PI)
Cisplatin-based chemotherapy is widely used in the treatment of advanced lung cancer with an approximate survival rate of 5 years

Summary

Introduction

Lung cancer is the most common cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 80∼85% of all lung cancers [1, 2]. Bu-ZhongYi-Qi decoction (BZYQD), called Bu-Zhong-Yi-Qi-Tang in China and Bojungikki-tang or Hochu-ekki-to in Japan, comprises crude ingredients that are extracted from eight herbs (Table 1). It is a well-known formula in traditional Chinese medicine identified as an effective medication to improve the quality of life and nutritional status of patients [4,5,6,7]. We evaluated the effect of BZYQD in combination with cisplatin on human non-small cell lung cancer cells and its possible drug-resistance reversal mechanism

Materials and Methods

Results

Discussion