Department of Urology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
Int J Oncol. 2017 Oct;51(4):1219-1226. doi: 10.3892/ijo.2017.4089. Epub 2017 Aug 2.
Because bladder cancer (BCa) is the 9th most common malignant tumor and 13th leading cause of death due to cancer, therapeutic approaches have attracted a great deal of attention from both clinicians and BCa patients. Although the development of surgery and targeted drugs has brought new challenges for the traditional concept of BCa therapy, various types of chemotherapy remain the final treatment method for many BCa patients. However, chemoresistance inevitably appears, leading to the failure of chemotherapy. Silibinin, a polyphenolic flavonoid component isolated from the fruits or seeds of milk thistle, has been reported to play important roles in inhibiting tumor chemoresistance in breast cancer and head and neck squamous cell carcinomas. Our previous study indicated that silibinin inhibited BCa progression in some mechanisms but with no conclusion of chemoresistance inhibition. Therefore, in the present study, we dissected the role of silibinin in BCa progression and chemoresistance. Our results revealed that in BCa, chemodrug-induced chemoresistance was reversed in the presence of silibinin. Further mechanistic study indicated that silibinin suppressed chemoresistance and BCa malignancy in an NF-κB-dependent and -independent manner. In addition, all of the inhibitory effects were dose‑dependent. Thus, our results provide a potential use for silibinin in BCa therapeutics.
由于膀胱癌（BCa）是第 9 大常见恶性肿瘤和第 13 大癌症死亡原因，因此治疗方法引起了临床医生和 BCa 患者的极大关注。尽管手术和靶向药物的发展为 BCa 治疗的传统观念带来了新的挑战，但各种类型的化疗仍然是许多 BCa 患者的最终治疗方法。然而，化疗耐药性不可避免地出现，导致化疗失败。水飞蓟素是从奶蓟的果实或种子中分离出来的一种多酚类黄酮化合物，已被报道在抑制乳腺癌和头颈部鳞状细胞癌的肿瘤化疗耐药性方面发挥重要作用。我们之前的研究表明，水飞蓟素通过一些机制抑制了 BCa 的进展，但没有得出抑制化疗耐药性的结论。因此，在本研究中，我们剖析了水飞蓟素在 BCa 进展和化疗耐药性中的作用。我们的结果表明，在 BCa 中，水飞蓟素的存在逆转了化疗药物诱导的化疗耐药性。进一步的机制研究表明，水飞蓟素以 NF-κB 依赖和非依赖的方式抑制化疗耐药性和 BCa 恶性程度。此外，所有抑制作用均呈剂量依赖性。因此，我们的结果为水飞蓟素在 BCa 治疗中的应用提供了一种潜在的用途。
