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Cancer Chemotherapy and Pharmacology

, Volume 56, Issue 4, pp 427–435 | Cite as

Neoadjuvant chemotherapy for epithelial ovarian cancer—role of apoptosis

  • Tania Dutta
  • Himani Sharma
  • Lalit Kumar
  • A. K. Dinda
  • Sunesh Kumar
  • Neerja Bhatla
  • Neeta SinghEmail author
Original Article

Abstract

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.

Keywords

Ovarian carcinoma Chemotherapy Apoptosis bcl-2 Survivin and p53 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Tania Dutta
    • 1
  • Himani Sharma
    • 1
  • Lalit Kumar
    • 4
  • A. K. Dinda
    • 2
  • Sunesh Kumar
    • 3
  • Neerja Bhatla
    • 3
  • Neeta Singh
    • 1
    Email author
  1. 1.Department of BiochemistryAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Department of PathologyAll India Institute of Medical SciencesNew DelhiIndia
  3. 3.Department of Obstetrics and GynecologyAll India Institute of Medical SciencesNew DelhiIndia
  4. 4.Institute Rotary Cancer HospitalAll India Institute of Medical SciencesNew DelhiIndia

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