The relationship between p53 status and anticancer drugs-induced apoptosis in nine human bladder cancer cell lines.
To study the relationship between the p53 status and chemotherapeutic drug-induced apoptosis, we have assessed the extent of apoptosis in nine bladder cancer cell lines during the treatment of adriamycin, cisplatin and methotrexate. Apoptosis was measured by the DNA fragmentation and merocyanine 540 (MC540) staining methods. Among the nine human bladder cancer cell lines, both wt-p53- and mut-p53-expressing cell lines (p53+/-) underwent apoptosis in response to anticancer drugs treatment. While the J82 (p53-/-) and TCCSUP (p53+/+) cell lines showed little or no apoptosis to these agents. Similar results were obtained when subjected to low doses of anticancer drug treatment. Interestingly, our results suggested that bladder cancer cells heterozygous for mutant p53 (+/-) seem to be most susceptible to chemotherapeutic drug. We therefore postulate that p53 mutations do not always provide a selective advantage in the development of chemoresistance, at least in bladderer tumor cell lines.
Chang
F L
FL
Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Lai
M D
MD
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology*; D002945:Cisplatin / Q000494:pharmacology; D004396:Coloring Agents; D053938:DNA Fragmentation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016158:Genes, p53; D006801:Humans; D008563:Membrane Lipids / Q000032:analysis; D008727:Methotrexate / Q000494:pharmacology; D010718:Phosphatidylserines / Q000032:analysis; D011744:Pyrimidinones; D014407:Tumor Cells, Cultured / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*
D000970:Antineoplastic Agents; D004396:Coloring Agents; D004273:DNA, Neoplasm; D008563:Membrane Lipids; D010718:Phosphatidylserines; D011744:Pyrimidinones; D016159:Tumor Suppressor Protein p53; C003954:merocyanine dye; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate