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.
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.
Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, 79 Chongshan Eastern Road, Huanggu District, Shenyang 110847, China; The First Clinical College, Liaoning University of Traditional Chinese Medicine, 79 Chongshan Eastern Road, Huanggu District, Shenyang 110847, China.
Ning
0000-0003-4972-4010
N
Yu
Department of Cell Biology, Basic Medical College, Liaoning University of Traditional Chinese Medicine, 79 Chongshan Eastern Road, Huanggu District, Shenyang 110847, China.
Ying
Y
Xiong
Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, 79 Chongshan Eastern Road, Huanggu District, Shenyang 110847, China; Department of Cell Biology, Basic Medical College, Liaoning University of Traditional Chinese Medicine, 79 Chongshan Eastern Road, Huanggu District, Shenyang 110847, China.
Chun
0000-0002-8167-0043
C
Wang
D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D029001:Herbal Medicine / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008516:Medicine, Chinese Traditional / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014867:Water
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; C402943:bu-zhong-yi-qi-tang; D014867:Water; D002945:Cisplatin