Related Experiment Videos
p53 gene status and chemosensitivity in ovarian cancer
1Department of Obstetrics and Gynecology, Tottori University, School of Medicine.
Abstract:
Recent studies suggest that drug induced apoptosis relates to the sensitivity. p53 gene, which has a pivotal role in inducing apoptosis, frequently mutates in ovarian cancer. Therefore, p53 gene status and chemosensitivity in epithelial ovarian cancer is discussed. Nonresponders to chemotherapy had mutations of the p53 gene more frequently (83% for nonresponders vs. 16% for responders) in patients with epithelial ovarian cancer undergoing platinum-base chemotherapy. Apoptotic index was significantly greater in tumors with wild-type p53 gene than those without the gene. p53 gene transduction markedly enhanced the sensitivity to cisplatin (CDDP) and CDDP-induced apoptosis, but did not affect the sensitivity to paclitaxel (PTX) nor PTX-induced apoptosis in ovarian cancer cells without p53 gene. The combination treatment with a recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) and CDDP significantly suppressed tumor growth of ovarian cancer cells with and without p53 gene, compared with a single treatment of either AxCAp53 or CDDP in ovarian cancer xenograft. Apoptotic index was significantly higher and proliferating cell nuclear antigen labeling index was relatively lower in an ovarian cancer xenograft without p53 gene receiving combination treatment, compared with a single treatment of either CDDP or AxCAp53, suggesting that the transduction of p53 gene induces apoptosis, but does not enhance the DNA repair system. A significant survival advantage was observed in the combination treatment compared with other treatments in carcinoma peritonitis models. In conclusion, p53 gene status contributes the sensitivity to CDDP in ovarian cancer. Additionally, combination treatment of p53 gene transduction and CDDP may be an effective therapeutic modality for ovarian cancer without wild-type p53 gene.
Insights
p53 gene status impacts ovarian cancer sensitivity to chemotherapy. Restoring wild-type p53 gene with cisplatin shows promise for treating ovarian cancer, especially in tumors lacking the p53 gene.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p53 gene plays a crucial role in apoptosis and is frequently mutated in ovarian cancer.
- p53 gene status is increasingly recognized as a factor influencing chemosensitivity in epithelial ovarian cancer.
Purpose of the Study:
- To investigate the relationship between p53 gene status and chemosensitivity in epithelial ovarian cancer.
- To evaluate the efficacy of p53 gene transduction combined with chemotherapy in ovarian cancer models.
Main Methods:
- Analysis of p53 gene mutations in nonresponder and responder ovarian cancer patients undergoing platinum-based chemotherapy.
- Assessment of apoptotic index in tumors with wild-type versus mutated p53.
- In vitro studies on ovarian cancer cells to determine the effect of p53 gene transduction on sensitivity to cisplatin (CDDP) and paclitaxel (PTX).
- In vivo studies using ovarian cancer xenografts and carcinoma peritonitis models to evaluate combination therapy with a recombinant adenovirus carrying wild-type p53 (AxCAp53) and CDDP.
Main Results:
- Nonresponders to chemotherapy exhibited a higher frequency of p53 gene mutations (83%) compared to responders (16%).
- Tumors with wild-type p53 showed a significantly greater apoptotic index than those without.
- p53 gene transduction enhanced sensitivity to CDDP and CDDP-induced apoptosis but not to PTX.
- Combination treatment with AxCAp53 and CDDP significantly suppressed tumor growth and increased apoptosis in ovarian cancer xenografts, outperforming single treatments.
- Combination therapy led to a significant survival advantage in carcinoma peritonitis models.
Conclusions:
- p53 gene status is a significant determinant of CDDP sensitivity in ovarian cancer.
- Combining p53 gene transduction with CDDP represents a potential therapeutic strategy for ovarian cancer, particularly for tumors with wild-type p53.
- The p53 gene transduction primarily induces apoptosis and does not appear to enhance the DNA repair system.