辣椒素抑制基質金屬蛋白酶-11影響的膀胱腫瘤惡性轉移的機制

蔡德甫¹、黃一勝^1,3,4、仇光宇¹、何肇晏¹、張安辰²

¹新光醫院 泌尿科，²轉譯醫學中心；³台北醫學大學 醫學院；⁴輔仁大學 醫學院

The Role of Capsaicin in Inhibiting Bladder Tumor Metastasis through the Regulation of Matrix Metalloproteinase-11 Expression

Te-Fu Tsai ¹, Thomas I-Sheng Hwang^1,3,4, Kuang-Yu Chou¹, Chao-Yen Ho¹and An-Chen Chang²

Department of Urology¹ and Translational Medicine Center², 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 a prevalent malignant tumor of the urogenital tract, ranking second only to prostate cancer in incidence. Matrix metalloproteinases (MMPs) have been found to play a role in the progression of numerous cancers. Among the MMP family, matrix metalloproteinase 11 (MMP11) is involved in extracellular matrix degradation and has been linked to cancer progression. The literature found that capsaicin inhibits cell survival, reduces inflammation, and promotes cell apoptosis. However, the role of capsaicin affects tumor progression in BC is unclear.

Materials and Methods:

We used the UALCAN online database to assess the performance and prognostic value of MMP11 mRNA in BC patients. Additionally, we purchased a BC tissue microarray from US Biomax to investigate the protein expression of MMP11 via immunohistochemistry staining. In vitro cell migration was performed to analyze the role of MMP11 in regulating cell motility in BC cells. An in vivo animal model was used to analyze the potential of capsaicin in inhibiting the tumor growth of BC.

Results:

Our findings demonstrate that MMP11 mRNA is overexpressed in BC tissues, and its expression is positively correlated with clinical stage, distal lymph node metastasis, malignancy, and poor overall survival rate. Furthermore, immunohistochemistry staining revealed that MMP11 protein levels were higher in BC tumor tissues than in stromal and normal tissues. In vitro analysis using siRNA showed that MMP11 blockade reduced cell migratory and invasive activity. Using a Transwell system, we selected a metastatic subpopulation from the human BC cell line T24 (T24-M) and found that T24-M cells had higher MMP11 expression compared to T24 wild-type cells. Interestingly, we further found that capsaicin inhibited cell motility, MMP11 protein and mRNA expression in a dose-dependent manner. Further studies confirmed that capsaicin suppressed MMP11 expression through the TRPV1 receptor and its downstream p38/ERK/c-Jun signaling pathway. Finally, an in vivo animal model was performed which found that capsaicin inhibited the tumor growth of BC.

Conclusions: 

Taken together, our findings emphasize the importance of capsaicin as a novel MMP11 inhibitor and a potential to inhibit tumor progression in BC.