The establishment of a growth-controllable orthotopic bladder cancer model through the down-regulation of c-myc expression

// Ho Kyung Seo 1, 2 , Seung-Phil Shin 2 , Na-Rae Jung 2 , Whi-An Kwon 3 , Kyung-Chae Jeong 4 and Sang-Jin Lee 2 1 Center for Prostate Cancer, Hospital, National Cancer Center, Goyang, Gyeonggi-do, Korea 2 Genitourinary Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Korea 3 Department of Urology, School of Medicine, Institute of Wonkwang Medical Science, Wonkwang University, Wonkwang University Sanbon Hospital, Gunpo, Gyeonggi-do, Korea 4 Biomolecular Function Research Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Korea Correspondence to: Sang-Jin Lee, email: leesj@ncc.re.kr Ho Kyung Seo, email: seohk@ncc.re.kr Keywords: bladder cancer, c-myc, orthotopic bladder cancer model, MBT-2 Received: April 20, 2016 Accepted: June 17, 2016 Published: July 22, 2016 ABSTRACT To properly evaluate the biological effects of immunotherapy, it is critical to utilize a model of cancer in immune-competent mice. Currently, MBT-2 is the most common murine bladder cancer cell line used in orthotopic bladder cancer models, even though this cell type often has an inappropriate genetic mutation landscape. In these models, after tumors are detected with in vivo imaging, the mouse usually dies within two to three weeks due to post-renal azotemia caused by the rapidly growing mass. This event prohibits the evaluation of tumor behavior upon intravesical drug treatment. We explored whether an shRNA-induced decrease in the expression of the c-myc oncogene in MBT-2 cells could slow down their in vitro proliferation and in vivo tumor growth. We transduced MBT-2 cells with shRNA lentiviruses that bound c-myc, established MBT2.cMYCshRNA and confirmed the retardation of the growth of tumors implanted in C3H/He mice. Accordingly, this study suggests that this novel orthotopic bladder cancer model in immune-competent mice may be more appropriate for the analysis of the effects of the intravesical instillation of immunotherapeutic agents.