Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines
| Autor: | Godefridus J. Peters, Jaap Haveman, Chris van Bree, Natasja Castro Kreder, Willem J.P Loves, Nicolaas A. P. Franken |
|---|---|
| Přispěvatelé: | Center of Experimental and Molecular Medicine, Radiotherapy |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Lung Neoplasms Paclitaxel Antineoplastic Agents Deoxycytidine Radiation Tolerance Carcinoma Non-Small-Cell Lung Deoxycytidine Kinase medicine Tumor Cells Cultured Humans Radiology Nuclear Medicine and imaging Radiosensitivity Clonogenic assay Cisplatin Radiation Cell growth business.industry Deoxycytidine kinase Cell cycle Gemcitabine Oncology Drug Resistance Neoplasm Cytarabine Cancer research business medicine.drug |
| Zdroj: | International journal of radiation oncology, biology, physics, 54(1), 237-244. Elsevier Inc. |
| ISSN: | 0360-3016 |
| DOI: | 10.1016/s0360-3016(02)02891-2 |
| Popis: | Purpose : To determine cross-resistance to anti-tumor treatments in 2′,2′difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials : Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel, 5-fluorouracil (5-FU), methotrexate (MTX), cytarabine (ara-C), and dFdC was measured by a proliferation assay. Radiosensitivity and radioenhancement by dFdC of this cell panel and the human ovarian carcinoma cell line A2780 and its dFdC-resistant variant AG6000 were determined by clonogenic assay. Bivariate flowcytometry was performed to study cell cycle changes. Results : In the SWg, a complete deoxycytidine kinase (dCK) deficiency was found on mRNA and protein level. This was accompanied by a 10-fold decrease in dCK activity which resulted in the >1000-fold resistance to dFdC. Sensitivity to other anti-tumor drugs was not altered, except for ara-C (>100-fold resistance). Radiosensitivity was not altered in the dFdC-resistant cell lines SWg and AG6000. High concentrations (50–100 μM dFdC) induced radioenhancement in the dFdC-resistant cell lines similar to the radioenhancement obtained at lower concentrations (10 nM dFdC) in the parental lines. An early S-phase arrest was found in all cell lines after dFdC treatment where radioenhancement was achieved. Conclusions : In the dFdC-resistant lung tumor cell line SWg, the deficiency in dCK is related to the resistance to dFdC and ara-C. No cross-resistance was observed to other anti-tumor drugs used for the treatment in lung cancer. Sensitivity to ionizing radiation was not altered in two different dFdC-resistant cell lines. Resistance to dFdC does not eliminate the ability of dFdC to sensitize cells to radiation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|