Aiduqing formula suppresses breast cancer metastasis via inhibiting CXCL1-mediated autophagy |
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| Institution: | 1. The Research Center of Integrative Cancer Medicine, Discipline of Integrated Chinese and Western Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China;2. State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Chinese Medicine, Chengdu, Sichuan, China;3. The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China;4. Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, West China School of Pharmacy, Sichuan University, Chengdu, China;5. Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China;6. Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China;1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan;2. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan;3. School of Medicine, Chung Shan Medical University, Taichung, Taiwan;4. Department of Orthopedics, Chung Shan Medical University Hospital, Taichung, Taiwan;5. Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan;6. Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan;7. Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan;1. Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, 43000 Kajang, Bandar Sungai Long, Selangor, Malaysia;2. Faculty of Medicine, Universiti Teknologi Malaysia, Sungai Buloh, Selangor, Malaysia;1. Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China;2. College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety/Key Laboratory of Grains and Oils Quality Control and Processing, Nanjing University of Finance and Economics, Nanjing 210023, China;3. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China;1. Department of Gastrointestinopancreatic Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China;2. Gastric Cancer Center of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China;3. Indiana University School of Medicine, South Bend, and IU Health Goshen Center for Cancer Care, 200 High Park Avenue, Goshen, IN 46526, USA;4. Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA |
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| Abstract: | BackgroundMetastasis is the most common lethal cause of breast cancer-related death. Recent studies have implied that autophagy is closely implicated in cancer metastasis. Therefore, it is of great significance to explore autophagy-related molecular targets involved in breast cancer metastasis and to develop therapeutic drugs.PurposeThis study was designed to investigate the anti-metastatic effects and autophagy regulatory mechanisms of Aiduqing (ADQ) formula on breast cancer.Study Design/MethodsMultiple cellular and molecular experiments were conducted to investigate the inhibitory effects of ADQ formula on autophagy and metastasis of breast cancer cells in vitro. Meanwhile, autophagic activator/inhibitor as well as CXCL1 overexpression or interference plasmids were used to investigate the underlying mechanisms of ADQ formula in modulating autophagy-mediated metastasis. Furthermore, the zebrafish xenotransplantation model and mouse xenografts were applied to validate the inhibitory effect of ADQ formula on autophagy-mediated metastasis in breast cancer in vivo.ResultsADQ formula significantly inhibited the proliferation, migration, invasion and autophagy but induced apoptosis of high-metastatic breast cancer cells in vitro. Similar results were also observed in starvation-induced breast cancer cells which exhibited elevated metastatic ability and autophagy activity. Mechanism investigations further approved that either CXCL1 overexpression or autophagic activator rapamycin can significantly abrogated the anti-metastatic effects of ADQ formula, suggesting that CXCL1-mediated autophagy may be the crucial pathway of ADQ formula in suppressing breast cancer metastasis. More importantly, ADQ formula suppressed breast cancer growth, autophagy, and metastasis in both the zebrafish xenotransplantation model and the mouse xenografts.ConclusionOur study not only revealed the novel function of CXCL1 in mediating autophagy-mediated metastasis but also suggested ADQ formula as a candidate drug for the treatment of metastatic breast cancer. |
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