Suppressive Effect of Matrine on Tumor Invasion in N-Butyl-N-(4-Hydroxybutyl)Nitrosamine-Induced Urinary Bladder Carcinogenesis

Abstract

Aims: This study was designed to investigate the mechanisms and suppressive effects of matrine on the development of urinary bladder cancers induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. Methods: Male Sprague-Dawley rats were given BBN (200 mg/rat) twice a week for a period of 8 weeks. Oral administration of matrine (50 and 100 mg/kg) was started 1 week before BBN exposure for 35 weeks. Half of each bladder was histopathologically analyzed and the remainder was extracted for protein analysis by Western blot. Results: The bladders of BBN-treated rats demonstrated progression from epithelial hyperplasia to papillary urothelial neoplasia and even poorly differentiated invasive cancer. Matrine (50 and 100 mg/kg) treatment decreased the formation of large bladder tumors by 31.6 and 21.1%, respectively. An incidence of cancer cells was detected in rats given BBN [70% (14/20)] and matrine [50 mg/kg: 68.4% (13/19) and 100 mg/kg: 57.9% (11/19), respectively]. The frequency of invasive tumors in the matrine treatment groups [50 mg/kg: 15.4% (2/13), 100 mg/kg: 9.1% (1/11)] was significantly lower than in the BBN-alone group [57% (8/14)]. Furthermore, oral administration of matrine (50 and 100 mg/kg) markedly attenuated the BBN-induced upregulation of bladder cyclooxygenase-2 (COX-2) expression and the elevation of bladder cytosolic phospholipase A2 (cPLA2) levels. Although the contents of 15-prostaglandin dehydrogenase (PGDH), which degrades PGE₂, were dramatically reduced by BBN, matrine exerted no effects on reduced PGDH contents. Conclusion: Our results suggest that matrine suppressed bladder tumor invasion in a rat model, and this might be primarily mediated through regulation of the protein contents, COX-2 and cPLA2 in the bladder.

Matrine inhibits the proliferation of pituitary tumor cells by decreasing Foxo3a phosphorylation and promoting Foxo3a nuclear localization

“…The results demonstrated that matrine had potent antitumor activity in pituitary cancer cells. This was consistent with the results that matrine suppressed bladder tumor invasion in a rat model, which could be primarily mediated by regulating the expression of COX-2 and cPLA2 in the bladder (17). Furthermore, we explored the molecular mechanism of matrine in pituitary cancer cells by western blotting analysis.…”

Matrine combined with cisplatin synergistically inhibited urothelial bladder cancer cells via down-regulating VEGF/PI3K/Akt signaling pathway

“…It has been confirmed that matrine could suppress the proliferation of numerous cancer cells in vitro, such as lung cancer [ 6 ], gastric cancer [ 7 ], liver cancer [ 8 ], breast cancer [ 9 ] and bladder cancer [ 10 ] cells. However, the anti-cancer effect of matrine is too weak to be used in antineoplastic chemotherapy alone.…”

<p>Matrine Restrains Cell Growth and Metastasis by Up-Regulating LINC00472 in Bladder Carcinoma</p>

“…28 More interesting, in an animal model of bladder tumor, Gao et al pointed out that MAT could suppress bladder tumor invasion via regulation of the cyclooxygenase-2 (COX-2), and cytosolic recombinant phospholipase A2 (cPLA2). 29 MAT treatment induced the inhibition of cell proliferation and invasion of bladder cancer, which was mediated by the PI3K/AKT signaling pathway, in vitro. 14 At the same time, a research displayed that MAT restrained prostate carcinoma, which was another kind of carcinoma of the urinary system.…”