Boosting bladder cancer treatment by intravesical nitazoxanide and bacillus calmette-guérin association.

Nitazoxanide (NTZ) has shown a promising antitumoral effect, the current study compared the anti-neoplastic effects of intravesical NTZ and BCG plus NTZ in NMIBC animal model.

30 rats, Fisher 344 were instilled with 4 intravesical doses of 1. 5 mg/kg of N-methyl-N-nitrosourea (MNU) every 15 days for BC induction. The animals were divided into 3 groups (Group BCG 106 UFC - 1 mg of BCG; Group NTZ - 300 mg/kg of NTZ; Group NTZ + BCG - simultaneous treatment of BCG and NTZ) and received weekly intravesical treatment for 6 consecutive weeks. Animals were submitted to ultrasound imaging and euthanasia, their bladders were collected and histopathological, immunohistochemical tests (ki67 e c-Myc) and Western Blotting (PI3K, mTOR, and p-4E-BP) were performed.

Histopathological tests showed 66.67%, 62.5% and 37.5% incidence of BC in animals treated with BCG, NTZ, and NTZ + BCG, respectively. Nuclear positivity for ki-67 in BC animals were 12.4% (IC 10.1-14.6%), 13.2% (IC 10.5-15.9%) and 8.8% (IC 6.0-11.6%) in BCG, NTZ and NTZ + BCG group, respectively (p = 0.063). Between animals with carcinoma, c-Myc strong positive was 40.10% in NTZ, 32.2% in BCG and 19.90% in the NTZ + BCG group (p < 0.001). Blotting has shown mTOR (p = 0.0473) and PI3K inhibition (p = 0.0349) in the presence of BCG, added to 4-EBP inhibition in the presence of NTZ (p = 0.0004).

Results show the possible synergy between the gold standard BC treatment BCG and NTZ, in which multiple targets inhibition such as c-Myc and downstream mTOR, p-4E-BP and PI3K might play a role.

World journal of urology. 2020 Jun 02 [Epub ahead of print]

Isis G A Kiehl, Eduardo Riccetto, Ana C C Salustiano, Marina V Ossick, Karen L Ferrari, Heloisa B Assalin, Osamu Ikari, Leonardo O Reis

UroScience, University of Campinas, Unicamp, Campinas, São Paulo, Brazil., School of Medical Sciences, Pontifical Catholic University of Campinas (PUC-Campinas) and UroScience, University of Campinas (Unicamp), R. John Boyd Dunlop, s/n, Campinas, São Paulo, Brasil, CEP, 13060-904. .