合成的類黃酮WYC0209經由阻遏HDGF/c-src表現與上皮-間質轉化抑制尿路上皮癌細胞的侵犯性
葉碧雯1,2、尤亮恩1,2、李經家1,2、楊顓丞6、李威明1,2,5、吳永昌6、吳文正1,2,3,4*
高雄醫學大學 泌尿科1，高雄醫學大學附設醫院 泌尿科2，高雄市立大同醫院 泌尿科3，高雄醫學大學 醫學研究所4，衛福部屏東醫院 泌尿科5，高雄醫學大學 天然藥物研究所6
Synthetic Flavonoid WYC0209 Inhibits Urothelial Carcinoma Cell Invasion through Repressing HDGF/c-src Expression and Epithelial‑Mesenchymal Transition
Bi-Wen Yeh1,2, Liang-En Yu1,2, Ching-Chia Li1,2, Juan-Cheng Yang6, Wei-Ming Li1,2,4,5, Yang-Chang Wu6 and Wen-Jeng Wu1,2,3,4*
Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung1; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung2; Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung3; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung4; Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung5; Graduate institute of natural products, Kaohsiung Medical University, Kaohsiung, Taiwan6
Purposes： Epithelial-to-mesenchymal transition (EMT) facilitates metastasis and drug resistance, both is the main causes of bladder urothelial carcinoma (UC) related death. In our previous studies in UCs, we found that HDGF overexpression is related to PI3K/Akt activation and induced EMT phenomenon, cancer stemness acquisition and drug resistance that rendered poorer outcome for patients. Here, we show that enforced expression of HDGF is sufficient to up-regulated of EMT markers expression, and then increase invasiveness of UC cells, which was rescued by natural flavonoid protoapigenone (WYC0209).
Materials and Methods: In the present study, we treated BFTC905 (bladder UC cell line) and BFTC909 (upper tract UC cell line) cells to investigate in this aspect, by using Western blot, MMT assay, migration/invasion assay and RT-PCR.
Results: The results of the present study demonstrated that WYC0209 significantly inhibited migration/invasion ability and decreased cell viability in both BFTC905 and BFTC909 cells. WYC0209 induced UC cells apoptosis via the inhibition of phosphrylation of AKT and increased caspase 3 activity. Mechanistically, WYC0209 treatment suppressed EMT by induction of E-cadherin and repression of c-src, IL6, Twist1, N-cadherin.
Conclusions: Our results showed that WYC0209 is a promising agent against UC cell invasion via downregulation of c-src and its target genes. Although further investigation is still warranted, our results highlight the potential beneficial of combination WYC0209 with current useful regimens (chemo-; immuno- agents) to enhance the therapeutic outcome of UC patients in the future.