Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Urol Oncol. 2014 Jan;32(1):36.e11-8. doi: 10.1016/j.urolonc.2013.02.013. Epub 2013 Aug 12.
Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA), a peritrichous P. aeruginosa strain with MSHA fimbriae, has been shown to be a valuable anticancer drug in many kinds of cancers. However, the effect of PA-MSHA on bladder cancer has not been elucidated. In this study, we focused on the antitumor activities and related mechanisms of PA-MSHA on bladder cancer in vitro and in vivo.
SV-40-immortalized normal uroepithelial cells (SV-HUC-1) and human bladder cancer cell lines (T24, 5637, and HT-1376) were treated with PA-MSHA or PA (heat-killed P. aeruginosa). At first, the effect of PA-MSHA on cancer cell proliferation was measured using Cell Counting Assay Kit-8 (CCK-8), whereas the changes of cell morphology were observed by transmission electron microscopy. The early apoptosis induced by PA-MSHA was evaluated by flow cytometry, and the expression level of apoptosis-related molecules was detected using Western blot assay. We then investigated the activation of the epidermal growth factor receptor signaling pathway stimulated by PA-MSHA; the expression and phosphorylation of several key regulators involved in the EGFR signaling pathway were detected. At last, xenograft tumor in nude mice was used to further investigate the antitumor effect of PA-MSHA in vivo.
Our results showed that PA-MSHA could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cell lines. Furthermore, cells stimulated with PA-MSHA exhibited an inactivation of EGFR signaling. In vivo, PA-MSHA treatment significantly suppressed tumor growth and induced apoptosis in xenografts tumor in nude mice.
PA-MSHA could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cells in vitro and in vivo, which is associated with the inactivation of EGFR signaling pathway, and it might be used as a potential therapeutic agent for bladder cancer.
铜绿假单胞菌甘露糖敏感血凝素（PA-MSHA）是一种具有 MSHA 纤毛的周生铜绿假单胞菌菌株，已被证明在多种癌症中是一种有价值的抗癌药物。然而，PA-MSHA 对膀胱癌的影响尚未阐明。在本研究中，我们专注于 PA-MSHA 在体外和体内对膀胱癌的抗肿瘤活性及相关机制。
SV-40 永生化正常尿路上皮细胞（SV-HUC-1）和人膀胱癌细胞系（T24、5637 和 HT-1376）用 PA-MSHA 或 PA（热灭活铜绿假单胞菌）处理。首先，通过 Cell Counting Assay Kit-8（CCK-8）测量 PA-MSHA 对癌细胞增殖的影响，而通过透射电子显微镜观察细胞形态的变化。通过流式细胞术评估 PA-MSHA 诱导的早期细胞凋亡，并用 Western blot 检测法检测凋亡相关分子的表达水平。然后，我们研究了 PA-MSHA 刺激的表皮生长因子受体信号通路的激活；检测了参与 EGFR 信号通路的几个关键调节因子的表达和磷酸化。最后，使用裸鼠异种移植肿瘤进一步研究 PA-MSHA 在体内的抗肿瘤作用。
我们的结果表明，PA-MSHA 可以有效地抑制人膀胱癌细胞系的增殖并诱导细胞凋亡。此外，用 PA-MSHA 刺激的细胞表现出 EGFR 信号通路的失活。在体内，PA-MSHA 处理显著抑制裸鼠异种移植肿瘤的生长并诱导肿瘤细胞凋亡。
PA-MSHA 可以有效地抑制人膀胱癌细胞在体外和体内的增殖并诱导细胞凋亡，这与 EGFR 信号通路的失活有关，它可能被用作膀胱癌的潜在治疗剂。
