Paeoniflorin inhibits the growth of bladder carcinoma via deactivation of STAT3.

Bladder cancer (BCa) is one of the most common urinary cancers. The present study aims to investigate whether Paeoniflorin (Pae) can exert inhibitory effects on BCa. The results showed that Pae inhibited proliferation of human BCa cell lines in a concentration- and time-dependent manner. Pae and cisplatin (Cis) synergistically inhibited the growth of tumours in RT4-bearing mice. Pae treatment neutralized the body loss induced by Cis. Moreover, Pae induced apoptosis in RT4 cells and increased the activities of caspase3, caspase8 and caspase9. Western blotting and immunohistochemical analysis revealed that the phosphorylated signal transducer and activator of transcription-3 (p-STAT3) level were decreased in Pae-treated RT4 cells and Pae-treated tumour-bearing mice. Furthermore, STAT3 transcriptional target B-cell lymphoma-2 was decreased in Pae-treated RT4 cells. Interestingly, Pae prevented translocation of STAT3 to the nucleus in RT4 cells. Collectively, Pae inhibits the growth of BCa, at least in part, via a STAT3 pathway.

Ginkgetin induces apoptosis in 786-O cell line via suppression of JAK2-STAT3 pathway.

OBJECTIVES: Renal cell carcinoma (RCC) is insensitive to conventional chemotherapy. Ginkgetin effectively treats several carcinoma cells. However, little is known about effects of Ginkgetin on RCC. In the present study, using 786-O cells, we evaluate whether Ginkgetin exerts anticancer effects against RCC. MATERIALS AND METHODS: 786-O cells suspended in the medium containing Ginkgetin were cultured for 24 hr to 72 hr, and then MTT assay was used to study cytotoxic effect of Ginkgetin. Apoptosis in 786-O was measured by an FITC Annexin apoptosis detection kit. Protein expression was detected by Western blotting. 786-O cells with active Janus kinase 2 (JAK2)-Signal transducer and activator of transcription 3 (STAT3) were prepared by stimulant of interleukin-6 (IL-6), whereas 786-O cells with deactivated STAT3 were produced by small interfering RNA (siRNA) STAT3. RESULTS: Ginkgetin suppressed the growth of 786-O in dose and time-dependent manners with IC50 values of 7.23 µM. Ginkgetin induced apoptosis of 786-O cells and increased the levels of caspase-8, caspase-9, and caspase-3. Additionally, Ginkgetin treated 786-O cells showed decreased levels of JAK2 and phosphorylated-STAT3 whether or not IL-6 was pretreated. Interestingly, pretreatment of siRNA STAT3 exerted inhibitory effects on the growth of 786-O cells, and the observation could be further reinforced after the Ginkgetin treatment. CONCLUSION: Our results indicate Ginkgetin possesses obvious inhibitory effects on the proliferation of 786-O, and this effect is probably due to its inhibition of JAK2/STAT3 pathway. Our findings imply Ginkgetin is a potential therapeutic medicine for RCC.

Cantharidin induces G2/M arrest and triggers apoptosis in renal cell carcinoma.

The present study aimed to investigate the effects of cantharidin on cell cycle distribution, the induction of apoptosis, and Notch1 and Jagged1 expression in ACHN and Caki­1 renal cancer cells. Cell viability assay, flow cytometry, cell cycle and western blot analyses were performed for ACHN and Caki­1 cells. Immunohistochemistry was used to analyze the expression of Notch1 and Jagged1 in RCC tissues The results demonstrated that treatment with cantharidin exerted a dose­ and time­dependent effect on cell viability, apoptosis induction and G2/M phase cell cycle arrest. Exposure of ACHN and Caki­1 cells to 20 µM cantharidin reduced cell viability to 26 and 32% respectively, after 48 h. In addition, treatment with cantharidin enhanced the number of ACHN and Caki­1 cells in G2/M phase to 54.62 and 51.88% respectively, as compared with 17.16 and 16.53% in the control groups. In the ACHN and Caki­1 cells, treatment with cantharidin induced a marked increase in the proportion of apoptotic cells after 48 h. Furthermore, cantharidin enhanced the percentage ACHN and Caki­1 apoptotic cells to 57.23 and 62.34% respectively, as compared with 2.27 and 3.06% in the control groups. Detection of Notch1 and Jagged1 expression demonstrated that levels were significantly increased in carcinoma tissues. Conversely, cantharidin exhibited an inhibitory effect on Notch1 and Jagged1 expression after 48 h. Therefore, treatment with cantharidin may exert a promising effect on the inhibition of renal cancer, and may be of therapeutic importance for the treatment of renal cancer.