Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C. Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
Anticancer Res. 2014 Jun;34(6):2973-83.
Urothelial cancer (UC) is a common cancer among males. Once metastatic or chemoresistant diseases develop, there is little effective treatment available. A fungal immunomodulatory protein, ganoderma tsugae (FIP-gts) possesses antitumor activity against solid tumors and inhibits telomerase activity. FIP-gts induces autophagy in cancer cells and may provide an alternative pathway against chemo-resistance.
Two UC cell lines were used to investigate the cytotoxicity effects and the autophagy regulation of FIP-gts using flow cytometry, acidic vesicular organelles (AVO) staining and western blotting.
MTT assay showed that FIP-gts and bafilomycin-A1 (Baf-A1) and or chloroquine (CQ) could enhance a significantly synergistic cytotoxicity. The treatment of UC cell lines with FIP-gts activated LC-3 II formation and AVO positive staining on western blot and flow cytometry. Interestingly, FIP-gts and Baf-A1 combined treatment was found to lead to enhancement of apoptosis along with inhibition of autophagy in parental and resistant UC cells.
FIP-gts may have the potential to be utilized as a therapeutic adjuvant for the treatment of resistant UC cancer down-regulating Beclin-1 to activate autophagic cell death.
膀胱癌（UC）是男性中常见的癌症。一旦发生转移性或耐药性疾病，有效的治疗方法就很少。一种真菌免疫调节蛋白，云芝糖肽（FIP-gts）对实体瘤具有抗肿瘤活性，并抑制端粒酶活性。FIP-gts 诱导癌细胞自噬，并可能为对抗化疗耐药性提供另一种途径。
使用流式细胞术、酸性囊泡细胞器（AVO）染色和 Western blot 分析，研究 FIP-gts 对 UC 细胞系的细胞毒性作用和自噬调控作用。
MTT 检测表明，FIP-gts 与巴弗洛霉素 A1（Baf-A1）和/或氯喹（CQ）联合使用可显著增强协同细胞毒性。FIP-gts 处理 UC 细胞系后，LC-3 II 形成和 AVO 阳性染色在 Western blot 和流式细胞术上均被激活。有趣的是，在亲本和耐药 UC 细胞中，FIP-gts 与 Baf-A1 联合处理可导致凋亡增强，同时抑制自噬。
FIP-gts 可能有潜力作为治疗耐药性 UC 癌症的辅助药物，通过下调 Beclin-1 激活自噬性细胞死亡。
