Cigarette smoke is a major risk factor for bladder cancer and contributes to chemoresistance in bladder cancer patients who continue to smoke while receiving chemotherapy. The main component in cigarette smoke, nicotine, can be detected in the urine of smokers. We present here a comprehensive review of recent investigations on nicotine's action in bladder cancer cell proliferation and chemoresistance. Transient nicotine stimulation activates Stat3/ERK1/2 and leads to the induction of Stat3 and NF-κB DNA binding activity, which is associated with cyclin D1 expression and cell proliferation in bladder cancer cells. Chronic nicotine exposure strongly activates Stat3, leading to cyclin D1 overexpression, cell cycle perturbations, and chemoresistance. Nicotine-induced cell proliferation and chemoresistance is mainly mediated by Stat3 and its downstream signals via the nicotinic acetylcholine receptor (nAChR) or the β-adrenoceptor (β-AR). Studying the mechanisms of nicotine-induced proliferation and chemoresistance may be helpful for the design of improved therapeutic strategies for bladder cancer patients. A chemotherapeutic strategy using pterostilbene seems feasible because pterostilbene can promote necrosis, autophagy, apoptosis and cell cycle arrest in both chemosensitive and chemoresistant bladder cancer cells. Thus the following recommendations for the chemoprevention of bladder cancer are presented: (1) cigarette smoking or nicotine-based treatment should be avoided to reduce bladder cancer incidence and chemoresistance, (2) α4/β2-nAChR, β-AR, and their downstream signaling pathways could be therapeutic targets for bladder cancer therapy, (3) pterostilbene is a promising chemopreventive agent for bladder cancer.

Original languageEnglish
Pages (from-to)252-256
Number of pages5
JournalJournal of Experimental and Clinical Medicine
Issue number6
Publication statusPublished - Dec 2011


  • Bladder cancer
  • Chemoprevention
  • Chemoresistance
  • Cigarette smoke
  • Nicotine
  • Pterostilbene

ASJC Scopus subject areas

  • General Medicine


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