The in vitro effect of paclitaxel on a LacZ-transfected malignant transitional cell line.
As bladder cancer is potentially lethal, the development of effective and tolerable therapeutic options is vital. In the present assay, we examined the in vitro effect of paclitaxel (Taxol) on the transitional cell carcinoma (TCC) cell line Hu1703He. Our model has several advantages over other in vitro models. The microenvironment in vivo is mimicked, and the important interaction between benign and malignant cells is consequently preserved in vitro. In addition, the results are not influenced by humoral immune factors. LacZ transfection and exposure to X-gal resulted in blue staining of the tumour cells and made them easy to visualise in sections. Tumour cell aggregates were cultured with continuous paclitaxel exposure to examine the drug's effect on tumour cell migration in monolayer and spheroidal growth in suspension culture. Paclitaxel treatment inhibited both tumour cell migration and spheroidal growth. Invasion was studied by confronting paclitaxel-treated and untreated tumour spheroids with benign bladder fragments in suspension culture. The co-cultures were followed for 4 weeks. Growth of the tumour cells encircling the bladder fragment and cellular infiltration of the bladder stroma were both inhibited by paclitaxel treatment. The expression of MMP-1 in tumour cells was also negatively influenced.
Vatne
Vendil
V
Department of Surgery, Haukeland University Hospital, University of Bergen, Norway. vendil.vatne@helse-bergen.no
Litlekalsoey
Jorunn
J
Wentzel-Larsen
Tore
T
Hostmark
Jens
J
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D018920:Coculture Techniques; D005434:Flow Cytometry; D006801:Humans; D007763:Lac Operon / Q000235:genetics*; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000494:pharmacology*; D018874:Spheroids, Cellular; D014162:Transfection; D001743:Urinary Bladder / Q000166:cytology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel