合成的類黃酮WYC0209能降低尿路上皮癌細胞的化療藥物抗藥性及幹細胞特性
葉碧雯1,2、尤亮恩1,2、李經家1,2,3、楊顓丞6、黃俊農1,2、李威明1,2,4,5、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 reduces drug resistant and stemness characters in urothelial cancer cells
Bi-Wen Yeh1,2, Liang-En Yu1,2, Ching-Chia Li1,2,3, Juan-Cheng Yang6, Chun-Nung Huang1,2, 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： Although cisplatin chemotherapy has improved outcome of urothelial carcinoma patients, the major challenge of treatment remains, mostly due to cancer stemness related chemoresistance. WYC0209 is a plant-derived natural flavonoid protoapigenone, isolated from Thelypteris torresiana, with a C-7 modification. Our previous study had demonstrated that WYC0209 enhance cisplatin chemosensitivity in urothelial bladder cancer.
Materials and Methods: In the present study, we treated T24 (bladder urothelial carcinoma cell line) and BFTC909 (upper tract urothelial carcinoma cell line) cells to investigate in this aspect, by using Western blot, MMT assay, Flow cytometry and RT-PCR.
Results: WYC0209 decreased cell viability and sphere formation in both T24 and BFTC909 cells. WYC0209 induced UC cells apoptosis via the inhibition of phosphrylation of AKT and increased caspase 3 activity. WYC0209 increased chemosensitivity were through downregulated CD133 (prominin-1) and ABCG2 (ATP-binding cassette sub-family G member 2) expressions.
Conclusions: Our results showed that WYC0209 exerts some beneficial potential in overcoming cisplatin drug resistance in urothelial carcinomas. We propose that by combination of WYC0209 and other useful regimens (chemo-; immuno- agents) may improve the therapeutic outcome of urothelial carcinoma patients in the future.