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Published on: November 2, 2014
Neoadjuvant chemotherapy for epithelial ovarian cancer--role of apoptosis
Tania Dutta1, Himani Sharma, Lalit Kumar
1Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Background:
Ovarian cancer is one of the most frequently fatal gynecological cancers because most cases are diagnosed at an advanced stage. Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumor progression. Little is known about the effect of various treatment regimens on the distribution of molecular markers of apoptosis in epithelial ovarian cancer. The objective of this study was to compare the expression levels of both proapoptotic and antiapoptotic proteins p53, p73, Bcl-2, Bcl-XL and survivin in the ascitic cells and tumor samples of patients undergoing treatment with two different regimens.
Methods:
A total of 24 patients with untreated epithelial ovarian cancer were randomized into two groups of 12 each. Group 1 patients received three cycles of chemotherapy prior to surgery and three cycles after surgery and group 2 patients received six cycles of chemotherapy prior to surgery. The expression of apoptosis-related proteins was analyzed in ascitic fluid and tumor samples by Western blotting and immunohistochemistry. The apoptotic index was also determined in these samples by the TUNEL assay.
Results:
Significant decreases in antiapoptotic bcl-2 and survivin were seen, accompanied by increases in apoptotic index in tumors that had undergone chemotherapy as compared to the baseline ascites samples. No significant change in bcl-XL was observed. A significant decrease in proapoptotic p53 was also seen. No expression of p73 was observed in tumors or ascites. The findings were similar in groups 1 and 2 patients and were not statistically significantly different, perhaps due to the small sample size (n=12) of each group.
Conclusions:
The above findings indicate that chemotherapy in ovarian carcinoma leads to an increase in apoptosis by a p53-independent pathway, which involves the downregulation of antiapoptotic Bcl-2 and survivin but not Bcl-XL. Furthermore, administering neoadjuvant chemotherapy (six cycles) as an alternative form of therapy for advanced epithelial ovarian cancer is more effective in inducing apoptosis than three cycles. However, the findings of this study need to be corroborated using a larger sample.
Insights
Chemotherapy for ovarian cancer increases apoptosis by reducing Bcl-2 and survivin, independent of p53. More cycles of neoadjuvant chemotherapy may be more effective in inducing apoptosis.
Area of Science:
- Gynecologic Oncology
- Cancer Biology
- Molecular Medicine
Background:
- Epithelial ovarian cancer is a leading cause of gynecological cancer mortality, often diagnosed at advanced stages.
- Tumor progression is driven by uncontrolled cell growth and resistance to apoptosis.
- The impact of chemotherapy on apoptosis-related molecular markers in ovarian cancer remains unclear.
Purpose of the Study:
- To compare the expression of proapoptotic (p53, p73) and antiapoptotic (Bcl-2, Bcl-XL, survivin) proteins in ovarian cancer patients.
- To evaluate the effect of two different chemotherapy regimens on these apoptosis markers.
Main Methods:
- 24 untreated epithelial ovarian cancer patients were randomized into two groups.
- Patients received either 3 cycles chemotherapy pre/post-surgery or 6 cycles pre-surgery.
- Apoptosis markers were analyzed using Western blotting, immunohistochemistry, and TUNEL assay.
Main Results:
- Chemotherapy decreased antiapoptotic Bcl-2 and survivin, increasing the apoptotic index.
- No significant change was observed in Bcl-XL expression.
- A decrease in proapoptotic p53 was noted; p73 was not expressed. Findings were similar between groups.
Conclusions:
- Chemotherapy induces apoptosis in ovarian cancer via a p53-independent pathway, downregulating Bcl-2 and survivin.
- Six cycles of neoadjuvant chemotherapy appear more effective in inducing apoptosis than three cycles.
- Larger studies are needed to confirm these findings.
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