title: CPA-7 influences immune profile and elicits anti-prostate cancer effects by inhibiting activated STAT3.
abstract: Platinum-based chemotherapy is emerging as the first line of treatment for castration resistant prostate cancer. Among the family of platinum (IV)-based compounds, a member known as CPA-7 inhibits the growth of multiple cancer cell lines. However, how and to what extent CPA-7 elicits its anti-prostate cancer effects in vivo is largely unknown.
  
  
  
  In this study, we firstly assessed the potential toxicity of the synthesized CPA-7 in a prostate cancer model as well as in normal mice. Next, we evaluated the in vitro effects of CPA-7 on the growth of prostate cancer cells using cell counting assay, and calculated the tumor sizes and cumulative survival rate of the tumor bearing mice by Kaplan-Meier method during CPA-7 treatment. Then we measured the expression level of the activated form of STAT3 (one targets of CPA-7) and its transcriptive activity post CPA-7 treatment by synergistically using western blot, IHC, and firefly luciferase reporter assays. Finally, effects of CPA-7 on immune cell trafficking in the tumor draining lymph nodes and in the spleens are evaluated with flow cytometry.
  
  
  
  Treatment with CPA-7 significantly inhibited growth of prostate cancer cells in vitro, and also in mice resulting in a prolonged survival and a decreased recurrence rate. These therapeutic effects are due, at least in part, to functional depletion of STAT3 in prostate tumor tissue as well as in the surrounding areas of tumor cell invasion. CPA-7 treatment also resulted in a reduced level of regulatory T cells and increased levels of cytotoxic T and T helper cells in the spleen and in tumor infiltrating lymph nodes. This favorable effect on immune cell trafficking may account for the amnestic immune response against recurrent prostate cancer.
  
  
  
  CPA-7 is a promising new therapeutic agent for prostate cancer that both inhibits tumor cell proliferation and stimulates anti-tumor immunity. It has potential as first line treatment and/or as an adjuvant for refractory prostate cancer.
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Liang
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150081, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhan
authors.affiliation: Biotherapy Center, Tumor Hospital of Harbin Medical University, Harbin, 150081, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Biotherapy Center, Tumor Hospital of Harbin Medical University, Harbin, 150081, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Biotherapy Center, Tumor Hospital of Harbin Medical University, Harbin, 150081, China.
authors.forename: Jiazi
authors.initials: J
authors.lastname: Wuyang
authors.affiliation: Biotherapy Center, Tumor Hospital of Harbin Medical University, Harbin, 150081, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Mu
authors.affiliation: Biotherapy Center, Tumor Hospital of Harbin Medical University, Harbin, 150081, China.
authors.forename: Dianjun
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150081, China. yanqiaozhang@126.com.
authors.forename: Yanqiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biotherapy Center, Tumor Hospital of Harbin Medical University, Harbin, 150081, China. xyhuang@hrbmu.edu.|Center of Translational Medicine, Harbin Medical University, Harbin, 150086, China. xyhuang@hrbmu.edu.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017606:Chlorine Compounds / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D008297:Male; D008810:Mice, Inbred C57BL; D017671:Platinum Compounds / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D017606:Chlorine Compounds; D017671:Platinum Compounds; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C529200:trichloronitritodiammineplatinum(IV)
keywords: CD4+ T cell; CPA-7; Prostate cancer; Regulatory T cell; STAT3