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Drug-Resistant Urothelial Cancer Cell Lines Display Diverse Sensitivity Profiles to Potential Second-Line Therapeutics.

Vallo S, Michaelis M, Rothweiler F, Bartsch G, Gust KM, Limbart DM, Rödel F, Wezel F, Haferkamp A, Cinatl J - Transl Oncol (2015)

Bottom Line: In one cell line with acquired resistance to gemcitabine (TCC-SUP(r)GEMCI(20)), cross-resistance seemed to be mediated by ABCB1 expression.Our model identified the vinca alkaloids vinblastine and vinflunine, in Europe an already approved second-line therapeutic for metastatic bladder cancer, as the most effective compounds in urothelial cancer cells with acquired resistance to gemcitabine or cisplatin.These results demonstrate that this in vitro model can reproduce clinically relevant results and may be suitable to identify novel substances for the treatment of metastatic bladder cancer.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Virology, University Hospital Frankfurt, Frankfurt am Main, Germany; Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany.

No MeSH data available.


Related in: MedlinePlus

Growth curves of urothelial carcinoma cell lines; 4000 cells per cm2 were seeded in cell culture flasks at day 0 containing IMDM supplemented with 10% FCS. Cell counts were determined using a Neubauer chamber in the presence of trypan blue. Values are displayed as mean ± SD. *P ≤ .05 relative to parental cell line.
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f0005: Growth curves of urothelial carcinoma cell lines; 4000 cells per cm2 were seeded in cell culture flasks at day 0 containing IMDM supplemented with 10% FCS. Cell counts were determined using a Neubauer chamber in the presence of trypan blue. Values are displayed as mean ± SD. *P ≤ .05 relative to parental cell line.

Mentions: Four of six gemcitabine-resistant sublines showed decreased growth rates compared to their parental cell lines [5637 (DT: 0.96 day) vs 5637rGEMCI20 (DT: 1.74 day); HT1376 (DT: 1.29 day) vs HT1376rGEMCI20 (DT: 1.74 day); TCC-SUP (DT: 2.05 day) vs TCC-SUPrGEMCI20 (DT: 4.91 day); T24 (DT: 0.97 day) vs T24rGEMCI20 (DT: 1.08 day)], while no significant differences were found for RT112 cells [RT112 (DT: 1.07 day) vs RT112rGEMCI20 (DT: 1.11 day)] and RT4 cells [RT4 (DT: 2.70 day) vs RT4rGEMCI10 (DT: 2.34 day)]. Three of six cisplatin-resistant sublines [RT112rCDDP1000 (DT: 0.96 day), RT4rCDDP1000 (DT: 1.65 day), and TCC-SUPrCDDP1000 (DT: 1.30 day)] displayed enhanced growth rates compared to their parental cell lines, while growth rate of 5637rCDDP1000 (DT: 1.23 day) cells was decreased relative to 5637 cells. For HT1376 vs HT1376rCDDP1000 (DT: 1.30 day) and T24 vs T24rCDDP1000 (DT: 1.03 day), no significant difference in growth rate was found (Figure 1).


Drug-Resistant Urothelial Cancer Cell Lines Display Diverse Sensitivity Profiles to Potential Second-Line Therapeutics.

Vallo S, Michaelis M, Rothweiler F, Bartsch G, Gust KM, Limbart DM, Rödel F, Wezel F, Haferkamp A, Cinatl J - Transl Oncol (2015)

Growth curves of urothelial carcinoma cell lines; 4000 cells per cm2 were seeded in cell culture flasks at day 0 containing IMDM supplemented with 10% FCS. Cell counts were determined using a Neubauer chamber in the presence of trypan blue. Values are displayed as mean ± SD. *P ≤ .05 relative to parental cell line.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4487788&req=5

f0005: Growth curves of urothelial carcinoma cell lines; 4000 cells per cm2 were seeded in cell culture flasks at day 0 containing IMDM supplemented with 10% FCS. Cell counts were determined using a Neubauer chamber in the presence of trypan blue. Values are displayed as mean ± SD. *P ≤ .05 relative to parental cell line.
Mentions: Four of six gemcitabine-resistant sublines showed decreased growth rates compared to their parental cell lines [5637 (DT: 0.96 day) vs 5637rGEMCI20 (DT: 1.74 day); HT1376 (DT: 1.29 day) vs HT1376rGEMCI20 (DT: 1.74 day); TCC-SUP (DT: 2.05 day) vs TCC-SUPrGEMCI20 (DT: 4.91 day); T24 (DT: 0.97 day) vs T24rGEMCI20 (DT: 1.08 day)], while no significant differences were found for RT112 cells [RT112 (DT: 1.07 day) vs RT112rGEMCI20 (DT: 1.11 day)] and RT4 cells [RT4 (DT: 2.70 day) vs RT4rGEMCI10 (DT: 2.34 day)]. Three of six cisplatin-resistant sublines [RT112rCDDP1000 (DT: 0.96 day), RT4rCDDP1000 (DT: 1.65 day), and TCC-SUPrCDDP1000 (DT: 1.30 day)] displayed enhanced growth rates compared to their parental cell lines, while growth rate of 5637rCDDP1000 (DT: 1.23 day) cells was decreased relative to 5637 cells. For HT1376 vs HT1376rCDDP1000 (DT: 1.30 day) and T24 vs T24rCDDP1000 (DT: 1.03 day), no significant difference in growth rate was found (Figure 1).

Bottom Line: In one cell line with acquired resistance to gemcitabine (TCC-SUP(r)GEMCI(20)), cross-resistance seemed to be mediated by ABCB1 expression.Our model identified the vinca alkaloids vinblastine and vinflunine, in Europe an already approved second-line therapeutic for metastatic bladder cancer, as the most effective compounds in urothelial cancer cells with acquired resistance to gemcitabine or cisplatin.These results demonstrate that this in vitro model can reproduce clinically relevant results and may be suitable to identify novel substances for the treatment of metastatic bladder cancer.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Virology, University Hospital Frankfurt, Frankfurt am Main, Germany; Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany.

No MeSH data available.


Related in: MedlinePlus