AICAR蛋白質能引發攝護腺癌細胞凋亡和抑制轉移是藉由著
AMP活化蛋白激酶和mTOR依賴的作用傳導路徑
蘇家震1,2 , 謝昆霖1 , 黃書彬3 , 黃冠華1 李佳陽 2
台南奇美醫學中心外科部 泌尿科1 高雄醫學大學醫學研究所2
高雄醫學大學泌尿部3
AICAR induces apoptosis and inhibits migration of prostate cancer cells through an AMPK/mTOR-dependent pathway
Chia-Cheng Su1,2,, Kun-Lin Hsieh1, , Shu-Pin Huang3, Kuan-Hua Huang1,
Chia-Yang Li2
1 Division of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan 71004, Taiwan.
2 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
3 Department of Urology, Kaohsiung Medical University Hospital and Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Purpose:
AICAR (5-aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells, 22RV1 cells.
Materals and Methods Cell growth was performed by MTT assay and soft agar assay. Cell apoptosis was examined by Annexin V/PI staining and PARP cleavage Western blot. Cell migration was evaluated by wound-healing assay. The expression of EMT-related protein and the activity of the AMPK/ mTOR-dependent pathway were analyzed by Western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay.
Results and Conclusions Our results indicated that AICAR inhibits cell growth, induces apoptosis, attenuates TGF-β-induced cell migration and EMT-related protein expression, and enhances the chemosensitivity to docetaxel through regulating the AMPK/mTOR-dependent pathway. Collectively, these findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.