Bladder cancer (BCa) is one of the most common malignancies in the western world. In the United States, it was estimated that there were 76,960 new cases and 16,390 deaths in 2016 (1). It was previously reported that approximately 30 % of BCa patients had muscle and invasive cancer cells and 10 % of patients suffered from metastatic disease, which re- sulted in a poor prognosis (2). Current application of chemotherapy, radiotherapy and radiochemotherapy has made great progress in preventing BCa, and the overall survival has been improved. However, recurrence and metastasis of BCa occurs frequently, leading to unsatisfactory survival rates. Moreover, poor prognosis has persisted due to fatigue, pain and side effects induced by chemotherapy (3). Thus, there is a demand to develop a safe and effective drug for improving treatment and prognosis of BCa patients.
Signal transducer and activator of transcription-3 (STAT3), one of the STAT family mem- bers, is a downstream effector of various cytokines, growth factors and hormones (4). Fol-lowing activation, phosphorylated STAT3 (p-STAT3) dimerizes and translocates to the nucleus, where it finally regulates the expression of numerous critical genes that control cell pro- liferation and survival (5–6). A number of studies have been performed on BCa, which have highlighted STAT3 as a potential therapeutic target. In clinical specimens, it has been con- firmed that urothelial BCa displays elevated expression as well as activation of STAT3 (7). Silencing of STAT3 suppresses the proliferation of T24 cells in vitro and in vivo compared to the controls, and overexpression of STAT3 prevents cells from undergoing morphological changes and apoptosis triggered by the Ha-ras oncogene (8–9). Moreover, inhibition of STAT3 by small interfering RNA or a specific inhibitor restores chemosensitivity in T24 cells (10), suggesting that STAT3 could be a major target for increasing chemosensitivity in patients.
Interest in the identification of novel anticancer agents derived from natural sources has been growing exponentially. Paeoniflorin (Pae) is the main active ingredient of Radix Paeoniae alba (RPA), which is used in traditional Chinese medicine to treat a range of in- flammatory diseases (11). Today, there is interest in studying the therapeutic effects of Pae on different cancer types. In previous pharmacological investigations, Pae was confirmed to inhibit the growth of human pancreatic cancer, gastric carcinoma cells, colorectal carci- noma cells, and glioma cells (12–15). A new study (16) recently reported the anti-prolifera- tive properties of RPA extraction in treating BCa, both in vitro and in vivo. However, it is unknown whether Pae could inhibit BCa. Therefore, the main purpose of the present study was to estimate the anti-tumour activity of Pae in BCa.
… A total of 2 × 103 cells were seeded in a 96-well plate and then incubated
with different concentrations of
Pae (purity > 98 %; Chengdu
Biopurify
Phytochemicals Ltd., China) for 24–72 h. The cells were treated with 20 µL …
