Exposure to Vinorelbine inhibits in vitro proliferation and invasiveness of transitional cell bladder carcinoma

BONFIL, RD, RUSSO, DM, SCHMILOVICH, AJ.

JOURNAL OF UROLOGY

American Urological Association

Año: 1996 vol. 156 p. 517 - 521

0022-5347

Abstract Purpose: To study the effect of vinorelbine (VNR) on in vitro cell proliferation, invasiveness, cell adhesion to substrate, cell motility and metalloproteinase secretion of MB-49, a murine transitional cell carcinoma of the bladder (TCC). Materials and Methods: The colorimetric MTS assay, which depends upon viable versus nonviable mitochondria, was used to evaluate the effect of graded concentrations of VNR on in vitro MB-49 cell growth. Chemoinvasion and cell motility were studied in TCC cells exposed for 24 hours to a noncytotoxic dose of VNR, through their ability to migrate across Matrigel -coated or Type IV collagen-coated 8-micrometer. pore filters. Zymographic studies in gelatin-embedded polyacrylamide gels were done to investigate gelatinolytic activity in conditioned media from treated and untreated MB-49 cells. Results: Vinorelbine inhibited MB-49 cell growth in a dose-dependent manner (IC50 40 ng./ml.). In vitro cell invasive capacity of MB-49 cells pretreated for 24 hours with VNR at noncytotoxic doses (1 and 10 ng./ml.) was significantly lower than that of untreated cells. The decreased invasion of VNR-treated cells was not accompanied by a diminished adhesion to Matrigel (R) or type IV collagen nor by a significant reduced secretion of gelatinolytic metalloproteinases. Instead, motility of MB-49 cells exposed to noncytotoxic concentrations of VNR was inhibited in a dose-response fashion similar to that of invasion. Conclusion: Vinorelbine proved to be an effective drug to inhibit tumor cell growth and invasion in a transitional cell bladder carcinoma model. The results obtained would justify preclinical studies to evaluate the effectiveness of VNR as a potential treatment of TCC. Key Words: bladder neoplasms; chemotherapy, adjuvant; neoplasm invasiveness