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Cross resistance and collateral sensitivity between cytotoxic drugs and radiation in two human bladder cell lines
O Pauwels1, M Gozy, P Van Houtte
1Laboratoire d'Histologie, Faculté de Médecine, Université Libre de Bruxelles, Belgium.
Abstract:
The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) test was employed as a means of studying the cross resistance and collateral sensitivities of two bladder cell lines able to grow in the presence of several antineoplastic drugs and/or despite the effects of radiotherapy. This cross resistance and collateral sensitivities were investigated in the context of two antineoplastic drugs (i.e. doxorubicin (an anthracycline) and vinorelbine (a Vinca alkaloid) and radiotherapy. The results show that cell lines able to grow in the presence of anticancer drugs develop a significant degree of resistance to antineoplastic compounds and may also develop resistance to radiotherapy. On the other hand, most cell lines treated first with radiotherapy develop a significant degree of resistance towards ionizing radiation and may also display increased sensitivity towards anticancer drugs. If these results obtained in vitro are clinically relevant, they may have important applications in the treatment of patients. Nevertheless, it will be necessary to validate the results on extensive series of chemo- and/or radioresistant cell lines exhibiting different mechanisms of resistance.
Insights
Cancer cells resistant to chemotherapy may also resist radiation therapy. Conversely, radiation-treated cells can become more sensitive to chemotherapy, suggesting new treatment strategies for bladder cancer.
Area of Science:
- Oncology
- Cell Biology
- Radiotherapy
Background:
- Chemotherapy and radiotherapy are standard cancer treatments.
- Drug resistance and radioresistance are major challenges in cancer therapy.
- Understanding cross-resistance and collateral sensitivity can optimize treatment protocols.
Purpose of the Study:
- To investigate cross-resistance and collateral sensitivity in bladder cancer cell lines.
- To examine the relationship between resistance to antineoplastic drugs and radiotherapy.
- To explore potential therapeutic implications of these resistance mechanisms.
Main Methods:
- Utilized the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay.
- Studied two bladder cancer cell lines with acquired resistance to antineoplastic agents.
- Assessed cross-resistance and collateral sensitivity to doxorubicin, vinorelbine, and radiotherapy.
Main Results:
- Cell lines resistant to anticancer drugs exhibited cross-resistance to chemotherapy and potentially radiotherapy.
- Cell lines initially treated with radiotherapy developed radioresistance and increased sensitivity to certain anticancer drugs.
- In vitro findings suggest complex interplay between drug resistance and radioresistance.
Conclusions:
- Acquired resistance to chemotherapy can confer resistance to radiotherapy in bladder cancer cells.
- Radiotherapy can induce collateral sensitivity to chemotherapy, offering therapeutic opportunities.
- Further validation in diverse resistant cell lines is crucial for clinical translation.