Format

Send to

Choose Destination
See comment in PubMed Commons below
Int J Oncol. 2014 Mar;44(3):883-95. doi: 10.3892/ijo.2014.2250. Epub 2014 Jan 8.

Combination of AG490, a Jak2 inhibitor, and methylsulfonylmethane synergistically suppresses bladder tumor growth via the Jak2/STAT3 pathway.

Author information

  • 1Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
  • 2Department of Surgery, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
  • 3Department of Urology, School of Medicine, Konkuk University Glocal Campus, Chungju 380-704, Republic of Korea.
  • 4Department of Biomedical Sciences, University College London, London, UK.
  • 5Genomic Informatics Center, Hankyong National University, Anseong 456-749, Republic of Korea.
  • 6Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
  • 7College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.

Abstract

Human urinary bladder cancer is the fifth most common cancer, with a worldwide estimate of about two million patients. Recurrence after complete transurethral prostatic resection is the most important problem in therapy. Combination therapy is a new approach in the treatment of cancers that do not respond to current therapies. These therapies have many advantages over conventional therapies, such as fewer side-effects and greater efficiency. Research efforts using natural compounds for the elimination or growth suppression of the cancer arise from studies on methylsulfonylmethane (MSM). MSM is a natural sulfur compound with no side-effects. AG490 is a tyrosine kinase inhibitor that has been extensively used for inhibiting Jak2 in vitro and in vivo. In our study, the combinatorial effect of these two agents on human bladder cancer cell lines and xenografts was analyzed. We observed that the combination of AG490 and MSM inhibited cancer cell viability and cell migration in vitro. This combination inhibited VEGF mRNA expression in bladder cancer cell lines. In vivo experiments showed that oral administration of AG490 and MSM combination significantly inhibited the growth of tumor xenografts in mice. Our study clearly demonstrates that the predominant effect of this combination is the reduction of signaling molecules including STAT3, STAT5b, IGF-1R, VEGF and VEGF-R2 which are involved in the growth, progression and metastasis of human bladder cancer. The anti-metastatic ability of this drug combination is confirmed using metastatic animal models. Therefore, this combination could have the effect of genesistasis and powerful anticancer effects against bladder cancer.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Spandidos Publications
    Loading ...
    Write to the Help Desk