氯奎與羥氯喹靶向MMP-2而降低膀胱癌的侵襲能力

仇光宇1、張安辰2、蔡德甫1、陳宏恩1、何肇晏1、黃一勝1,3,4

1新光醫院 泌尿科，2中央研究室；3台北醫學大學 醫學院；4輔仁大學 醫學院

The attenuation of chloroquine and hydroxychloroquine on the invasive potential of bladder cancer by targeting MMP-2 expression

Kuang-Yu Chou1, An-Chen Chang2, Te-Fu Tsai 1, Hung-En Chen 1, Chao-Yen Ho1 and Thomas I-Sheng Hwang1,3,4

Department of Urology1 and Central Laboratory2, Shin Kong Wu Ho-Su Memorial Hospital; Department of Urology, Taipei Medical University3; Division of Urology, School of Medicine, Fu-Jen Catholic University4, Taipei, Taiwan.

Purpose:

Bladder cancer (BC) is one of the most common urologic neoplastic disorders occurred in men with extremely lower survival rate caused by metastasis status. Chloroquine (CQ) and hydroxychloroquine (HCQ) are considered as an anticancer drug, can inhibit tumor progression and invasiveness. However, the clear mechanisms of CQ/HCQ effect on BC are undetermined.

Materials and Methods:

The immortalized uroepithelial cells (SV-HUC-1) and human BC cells (5637 and T24) were obtained from the Bioresource Collection and Research Center (BCRC; Hsinchu, Taiwan). Cell viability was assayed using resazurin reagent according to the manufacturer’s protocol (Biotium, Fremont, CA, USA). The migration and invasion assay were performed by using 24-transwell plates (8-μm pore size; Costar, NY, USA). Western blot was used to detect MMP2 protein expression after CQ or HCQ treatment for 24 h.

Results:

We found that CQ/HCQ are sensitive with bladder cancer cells. Importantly, CQ/HCQ has no such effect on normal cells suggesting CQ/HCQ can specify to target on BC. CQ/HCQ also interrupts the migrative and invasive ability of BC cells by inhibiting MMP2- belongs to matrix metalloproteinases (MMPs) family, also knowns as a key mediator of cancer progression. Moreover, further data revealed that the migrative and invasive effect by CQ or HCQ-treated cells was abolished after combining with Rapamycin- an activated autophagy factor, emphasis CQ/HCQ functions in BC based on autophagy inhibition. 

Conclusions:

In conclusion, our research demonstrated that representing of CQ/HCQ regulated the levels of cell motility in BC through reducing MMP2 expression via targeting autophagy functions, contributed a novel therapeutic strategy in future for treating patients suffered from the manifestation of this disease.