title: The Chinese medicine JC-001 enhances the chemosensitivity of Lewis lung tumors to cisplatin by modulating the immune response.
abstract: BACKGROUND
  JC-001 is a Chinese medicine that can modulate the immunity in Hepa 1-6 tumor-bearing mice, and we questioned whether JC-001 can serve as efficient adjuvant chemotherapy. We aimed to identify a novel approach for enhancing cis-diamminedichloroplatinum (II) (CDDP)-based chemotherapy by immunomodulation.
  
  
  METHODS
  The anti-tumor activity in vitro was determined based on foci formation and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A LLC1 tumor xenograft model was used to analyze the activity of tumor rejection in vivo. The tumors were analyzed through hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) staining and cytokine arrays.
  
  
  RESULTS
  JC-001 suppressed foci formation and reduced the viability of Lewis lung carcinoma (LLC1) cells in vitro. JC-001 suppressed LLC1 tumor growth in immunodeficient BALB/c nude mice and in immunocompetent C57BL/6 mice to an even greater extent. Furthermore, JC-001 up-regulated interferon-γ expression in the tumor microenvironment, enhanced the Th1 response in tumor-bearing mice, and increased the chemosensitivity of LLC1 tumors to CDDP chemotherapy. The results of our study suggest that JC-001 is associated with low cytotoxicity and can significantly suppress tumor growth by enhancing the Th1 response.
  
  
  CONCLUSIONS
  JC-001 is a Chinese medicine with potential clinical applications in CDDP-based chemotherapeutic regimens.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung City, 40201, Taiwan.
authors.forename: Meng-Hsien
authors.initials: MH
authors.lastname: Chuang
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, No.110, Sec.1, Jianguo N. Rd, Taichung City, 40201, Taiwan.|Immunology Research Center, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung City, 40201, Taiwan.|Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chung Shan Medical University Hospital, 110, Sec.1, Jianguo N. Rd, Taichung City, 40201, Taiwan.
authors.forename: Ming-Shiou
authors.initials: MS
authors.lastname: Jan
authors.affiliation: Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung City, 40201, Taiwan. jinghuat@csmu.edu.tw.|Department of Chest Medicine, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd, Taichung City, 40201, Taiwan. jinghuat@csmu.edu.tw.
authors.forename: Jinghua Tsai
authors.initials: JT
authors.lastname: Chang
authors.affiliation: Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung City, 40201, Taiwan. fjlu@csmu.edu.tw.|Department of Medical Research, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd, Taichung City, 40201, Taiwan. fjlu@csmu.edu.tw.
authors.forename: Fung-Jou
authors.initials: FJ
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D007371:Interferon-gamma; D002945:Cisplatin
keywords: CDDP; Chemosensitivity; Immune; Lung cancer