曼氏血吸蟲可溶性蟲卵抗原促使膀胱癌細胞的凋亡與焦亡

吳志緯¹、鄭柏青²、何承勳¹

1. 新光吳火獅紀念醫院外科部泌尿科

2. 臺北醫學大學醫學系分子寄生蟲暨熱帶疾病學科  

Schistosoma mansoni Soluble Egg Antigens Promote Apoptosis and Pyroptosis in Bladder Cancer Cells

Chih-Wei Wu ¹, Po-Ching Cheng ², Chen-Hsun Ho ¹

1.Divisions of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan;

2.Department of Molecular Parasitology and Tropical Diseases, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Purpose:

According to global epidemiological study, bladder cancer is the tenth most prevalent malignancy worldwide, with a substantially higher incidence in males. Typical clinical manifestations include hematuria, dysuria, and related lower urinary tract symptoms. For muscle-invasive bladder cancer, radical cystectomy remains the standard clinical intervention. Although this procedure effectively removes the tumor, it causes irreversible changes to the urinary tract and may adversely affect postoperative quality of life and survival. Consequently, the development of bladder-preserving adjuvant therapies, such as treatments that induce cancer cell apoptosis has emerged as an important research priority.

Apoptosis is widely recognized as a critical mechanism in cancer therapy. Previous studies have demonstrated that treatment with Schistosoma mansoni soluble egg antigens (SEAs) modulates caspase-3 activation through both intrinsic and extrinsic pathways, thereby triggering downstream apoptotic signaling. Pyroptosis, in comparison, is an inflammatory form of programmed cell death. Gasdermin D (GSDMD) functions as the key effector, its N-terminal fragment inserts into the plasma membrane to form pores after cleaved by caspase-1. then causing the efflux of activated IL-1β and IL-18, and leading to a strong inflammatory response. Pyroptosis has been also shown to suppress tumor progression and stimulate anti-tumor immunity.

Materials and Methods:

In this study, human bladder cancer cells (HTB-9) and normal human bladder epithelial cells (SV-HUC-1) were used as experimental models.

Results:

Following SEA treatment, HTB-9 cells exhibited markedly higher levels of apoptosis and pyroptosis than SV-HUC-1 cells, particularly at SEA concentrations of 12 and 16 µg/mL. Western blot analysis revealed a significant increase in caspase-3, caspase-8, caspase-9, and caspase-1 expression in HTB-9 cells compared with SV-HUC-1. Flow cytometry further confirmed a significant elevation in fluorescence-labeled caspase-1 and caspase-3 in HTB-9 cells, with pyroptosis predominating over apoptosis at equivalent SEA concentrations. Collectively, these data indicate that SEA strongly promotes pyroptosis and activation of inflammatory signaling in bladder cancer cells.

Conclusion:

Overall, this study elucidates the mechanism by which SEA induces apoptosis and pyroptosis in bladder cancer cells. These findings provide new perspectives for the development of bladder-preserving adjuvant therapies and may contribute to improved therapeutic strategies for bladder cancer.