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Published on: August 4, 2019
The relationship between p53 status and anticancer drugs-induced apoptosis in nine human bladder cancer cell lines
1Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Abstract:
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.
Insights
Bladder cancer cells with wild-type or mutant p53 showed apoptosis after chemotherapy. Cells heterozygous for mutant p53 were most susceptible, suggesting p53 mutations don't always confer chemoresistance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The p53 tumor suppressor protein plays a critical role in cellular responses to DNA damage, including apoptosis.
- Understanding the relationship between p53 status and chemosensitivity is crucial for optimizing cancer treatment strategies.
- Bladder cancer exhibits diverse p53 mutation profiles, influencing therapeutic outcomes.
Purpose of the Study:
- To investigate the correlation between p53 gene status (wild-type, mutant, or null) and the induction of apoptosis by common chemotherapeutic agents in human bladder cancer cell lines.
- To determine if specific p53 genotypes are associated with differential sensitivity to adriamycin, cisplatin, and methotrexate.
Main Methods:
- Utilized nine human bladder cancer cell lines with varying p53 statuses.
- Assessed apoptosis induction using DNA fragmentation assays and merocyanine 540 (MC540) staining.
- Treated cell lines with adriamycin, cisplatin, and methotrexate at various concentrations.
Main Results:
- Both wild-type p53 (p53+/+) and mutant p53 (p53+/-) expressing cell lines demonstrated apoptosis following treatment with anticancer drugs.
- Cell lines with a complete absence of p53 (p53-/-) or wild-type p53 showed minimal to no apoptosis.
- Bladder cancer cells heterozygous for mutant p53 (p53+/-) exhibited the highest susceptibility to chemotherapeutic agents, even at low doses.
Conclusions:
- p53 status significantly influences the apoptotic response of bladder cancer cells to chemotherapy.
- Heterozygous mutant p53 status appears to sensitize bladder cancer cells to common chemotherapeutic drugs.
- p53 mutations do not invariably confer a chemoresistance advantage in bladder tumor cell lines, challenging established paradigms.
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