title: Capsaicin enhances anti-proliferation efficacy of pirarubicin via activating TRPV1 and inhibiting PCNA nuclear translocation in 5637 cells.
abstract: The recurrence of bladder cancer after surgery with or without chemotherapy remains a major challenge in bladder cancer treatment. Previous studies have shown that transient receptor potential vanilloid 1 (TRPV1) acts as a tumor suppressor through inducing apoptosis in bladder cancer cells. However, whether activation of TRPV1 has any synergistic effects with pirarubicin (THP), one of main drugs used in urinary bladder instillation chemotherapy to improve chemotherapeutic efficacy has remained elusive. The present study verified that TRPV1 was differentially expressed in bladder cancer cell lines. Furthermore, activation of TRPV1 by capsaicin was shown to induce growth inhibition of 5637 cells in which TRPV1 was highly expressed, while the growth of T24 cells, which express TRPV1 at low levels, was not affected. In addition, the present study demonstrated that activation of TRPV1 enhanced the anti‑proliferative effects of pirarubicin using an MTT assay and cell cycle analysis. Finally, immunofluorescent microscopy revealed that activation of TRPV1 prevented the translocation of proliferating cell nuclear antigen to the nucleus. This phenomenon was reversed by pre‑treatment with capsazepine, a specific TRPV1 antagonist. In conclusion, the present study confirmed the anti‑tumor activity of TRPV1 against bladder cancer. Activation of TRPV1 may be applied as a novel strategy to treat bladder cancer or enhance the therapeutic efficacy of traditional chemotherapeutic drugs.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
mesh_terms: D006801:Humans; D002211:Capsaicin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D050916:TRPV Cation Channels / Q000819:agonists / Q000378:metabolism
chemical_list: D002211:Capsaicin; D004317:Doxorubicin; C027260:pirarubicin; D018809:Proliferating Cell Nuclear Antigen; D050916:TRPV Cation Channels; C494484:TRPV1 receptor