Enhanced chemosensitivity of bladder cancer cells to cisplatin by suppression of clusterin in vitro

Chung, Jinsoo; Kwak, Cheol; Jin, Ren Jie; Lee, Chang-Ho; Lee, Kang Hyun; Lee, Sang Eun

doi:10.1016/j.canlet.2003.07.008

« Previous Next »Cancer Letters
Volume 203, Issue 2 , Pages 155-161, January 2004

Enhanced chemosensitivity of bladder cancer cells to cisplatin by suppression of clusterin in vitro

Jinsoo Chung
- Urologic Oncology Clinic, National Cancer Center, Goyang, South Korea
Cheol Kwak
- Department of Urology, Seoul National University College of Medicine, Seoul National University Hospital, 28 Yongon Dong, Jongno Ku, Seoul, 110-744, South Korea
- Clinical Research Institute, Seoul National University Hospital, 28 Yongon Dong, Jongno Ku, Seoul, 110-744, Seoul, South Korea
Ren Jie Jin
- Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
Chang-Ho Lee
- Department of Urology, Soonchunhyang University College of Medicine, Cheonan, South Korea
Kang Hyun Lee
- Urologic Oncology Clinic, National Cancer Center, Goyang, South Korea
Sang Eun Lee
- Department of Urology, Seoul National University College of Medicine, Seoul National University Hospital, 28 Yongon Dong, Jongno Ku, Seoul, 110-744, South Korea
- Cancer Research Center, Clinical Research Institute, Seoul National University Hospital, 28 Yongon Dong, Jongno Ku, Seoul, 110-744, South Korea
- Corresponding author. Address: Department of Urology, Seoul National University College of Medicine, Seoul National University Hospital, 28 Yongon Dong, Jongno Ku, Seoul, 110-744, Seoul, South Korea. Tel.: +82-2-760-2408; fax: +82-2-742-4665

Received 24 February 2003; accepted 17 July 2003.

Abstract

We examined the functional role of clusterin in chemotherapy-induced apoptosis and tested whether anti-sense transfection targeted against clusterin enhances the chemosensitivity in human bladder cancer cells in vitro. Clusterin mRNA and protein expression of 253J cells, a human bladder carcinoma cell line, after treatment with cisplatin were measured by RT-PCR and Western blot analysis. Clusterin expression and cell growth were compared between 253J cells transfected with constructed a clusterin anti-sense plasmid vector (pCR-CLU-AS) and controls. Tumor cell viability was measured with MTT assay after cisplatin treatment. DNA fragmentation and CPP32 assay were performed. Clusterin expression was increased after treatment with cisplatin and highest at 8 h in 253J cells. Clusterin anti-sense transfectants were highly sensitive to apoptotic cell death induced by cisplatin compared with parental 253J cells or control transfectants. Collectively, our results showed that expression of clusterin was increased in the acute phase of cell death caused by cisplatin and that suppressing the expression of clusterin enhanced the susceptibility of apoptosis caused by cisplatin in human bladder cancer cells. These results suggest that lowering the expression of clusterin might increase the sensitivity of bladder cancer cells to chemotherapeutic agents.

Keywords: Clusterin, Anti-sense, Bladder cancer, Cisplatin, Chemosensitivity