前列腺癌誘發下尿路症狀病態生理機轉之動物模式研究

許齡內^1,2、蔡育賢³、蔡欣孜³、蘇文彬^2,4、唐一清³

¹臺南市立安南醫院–委託中國醫藥大學興建經營 泌尿科；²國立成功大學醫學院 臨床醫學研究所；³國立成功大學醫學院附設醫院 泌尿科；⁴國立成功大學醫學院附設醫院 內科部

Study on the pathophysiological mechanism responsible for lower urinary tract symptoms associated with prostate cancer using an animal model

Lin-Nei Hsu^1,2, Yuh-Shyan Tsai³, Hsin-Tzu Tsai³, Wen-Pin Su^2,4, Yat-Ching Tong³

¹ Department of Urology, An Nan Hospital, China Medical University, Tainan, Taiwan；² Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan；³ Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan；⁴ Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Purpose:

To investigate the pathophysiological mechanism leading to lower urinary tract symptoms in prostate cancer (PCa) by using an animal model.

Materials and Methods:

An orthotopic PCa model in mice was established by injection of human DU145 cells into the prostate gland lateral lobe of NOD-SCID mice. Cancer growth was quantified by luciferase-based in vivo imaging system (IVIS) serially every seven days. Comparisons were made for urodynamic parameters, bladder histology and biological markers until the sixth week. Bladder wall structural changes were assessed by the bladder wall thickness and degree of fibrosis. Biomarker expressions in bladder tissue including muscarinic M2 receptor, TRPV4, Bax and caspase3 were evaluated by immunohistochemical staining and immunofluorescence confocal laser scanning microscopy.

Results:

DU145 cell growth in the prostate were successfully monitored by luciferase-based IVIS. after orthotopic injection. Using our injection technique, no anatomical obstruction of the bladder outlet and urethra were noted up to six weeks after injection. The presence of PCa induced changes in urinary bladder histology, biomarkers and urodyanmic parameters. Cystometry showed features of detrusor overactivity with increased voiding frequency and high amplitude voiding contractions from the fourth week onward. Histological analyses four weeks after DU145 injection demonstrated detrusor thickening and bladder wall fibrosis. Immunohistochemistry showed increased expressions of bladder M2, TRPV4, Bax and caspase3 in the PCa mice as early as in the first or second week.

Conclusions:

PCa can induce bladder microenvironment changes involving neural receptors and biological mediators leading to histological and functional alterations even in the absence of overt anatomical obstruction.