Skip to main content

Advertisement

SpringerLink
Log in

Neoadjuvant chemotherapy for epithelial ovarian cancer—role of apoptosis

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Pettersson F (1991) Annual report on the results of treatment of gynecologic cancer. Int J Gynecol Obstet 36:238–277

    Article  Google Scholar 

  2. Richardson GS, Scully RE, Nikrui N (1985) Common epithelial cancer of the ovary. N Engl J Med 312:415–424

    CAS  PubMed  Google Scholar 

  3. Natarajan M, Saravanan SM, Elson DL (2003) Advanced ovarian carcinoma as a chronic disease: a case report and review. S D J Med 56:515–521

    PubMed  Google Scholar 

  4. See HT, Kavanagh JJ, Hu W, Bast RC (2003) Targeted therapy for epithelial ovarian cancer: current status and future prospects. Int J Gynecol Cancer 13:701–734

    Article  CAS  PubMed  Google Scholar 

  5. Mazzeo F, Berliere M, Kerger J, Squifflet J, Duck L, D’Hondt V, Humblet Y, Donnez J, Machiels JP (2003) Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy in patients with primarily unresectable, advanced-stage ovarian cancer. Gynecol Oncol 90:163–169

    Article  CAS  PubMed  Google Scholar 

  6. Gadducci A, Cosio S, Muraca S, Genazzani AR (2002) Molecular mechanisms of apoptosis and chemosensitivity to platinum and paclitaxel in ovarian cancer: biological data and clinical implications. Eur J Gynaecol Oncol 23:390–396

    CAS  PubMed  Google Scholar 

  7. Strasser A, O’Connor L, Dixit VM (2000) Apoptosis signaling. Annu Rev Biochem 69:217–245

    Article  CAS  PubMed  Google Scholar 

  8. Daponte A, Guidozi F, Tiltman AJ, Marineanu A, Taylor L (1999) p53 as a prognostic factor for stage III serous adenocarcinoma of the ovary. Anticancer Res 19:2387–2389

    CAS  PubMed  Google Scholar 

  9. Liu JR, Fletcher B, Page C, Hu C, Nunez G, Baker V (1998) Bcl-XL is expressed in ovarian carcinoma and modulates chemotherapy-induced apoptosis. Gynecol Oncol 70:398–403

    Article  CAS  PubMed  Google Scholar 

  10. Mano Y, Kikuchi Y, Yamamoto K, Kita T, Hirata J, Tode T, Ishii K, Nagata I (1999) Bcl-2 as a predictor of chemosensitivity and prognosis in primary epithelial ovarian cancer. Eur J Cancer 35:1214–1219

    Article  CAS  PubMed  Google Scholar 

  11. Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N (2000) Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res 6:127–134

    CAS  PubMed  Google Scholar 

  12. Zaffaroni N, Pennati M, Colella G, Perego P, Supino R, Gatti L, Pilotti S, Zunino F, Daidone MG (2002) Expression of the anti-apoptotic gene survivin correlates with taxol resistance in human ovarian cancer. Cell Mol Life Sci 59:1406–1412

    Article  CAS  PubMed  Google Scholar 

  13. Sharma H, Sen S, Mathur M, Bahadur S, Singh N (2004) Combined evaluation of expression of telomerase, survivin, and anti-apoptotic Bcl-2 family members in relation to loss of differentiation and apoptosis in human head and neck cancers. Head Neck 26:733–740

    Article  PubMed  Google Scholar 

  14. Lavarino C, Pilotti S, Oggionni M, Gatti L, Perego P, Bresciani G, Pierotti MA, Scambia G, Ferrandina G, Fagotti A, Mangioni C, Lucchini V, Vecchione F, Bolis G, Scarfone G, Zunino F (2000) p53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma. J Clin Oncol 18:3936–3945

    CAS  PubMed  Google Scholar 

  15. Gadducci A, Cianci C, Cosio S, Carnino F, Fanucchi A, Buttitta F, Conte PF, Genazzani AR (2000) p53 status is neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen. Anticancer Res 20:4793–4799

    CAS  PubMed  Google Scholar 

  16. Bergamaschi D, Gasco M, Hiller L, Sullivan A, Syed N, Trigiante G, Yulug I, Merlano M, Numico G, Comino A, Attard M, Reelfs O, Gusterson B, Bell AK, Heath V, Tavassoli M, Farrell PJ, Smith P, Lu X, Crook T (2003) p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. Cancer Cell 3:387–402

    Article  CAS  PubMed  Google Scholar 

  17. Alvarez AA, Lambers AR, Lancaster JM, Maxwell GL, Ali S, Gumbs C, Berchuck A, Futreal PA (2001) Allele loss on chromosome 1p36 in epithelial ovarian cancers. Gynecol Oncol 82:94–98

    Article  CAS  PubMed  Google Scholar 

  18. Chen CL, Ip SM, Cheng D, Wong LC, Ngan HY (2000) p73 gene expression in ovarian cancer tissues and cell lines. Clin Cancer Res 6:3910–3915

    CAS  PubMed  Google Scholar 

  19. Codegoni AM, Bertoni F, Patregnani C, Marinetti E, D’Incalci M, Broggini M (1999) Allelic expression of p73 in human ovarian cancers. Ann Oncol 10:949–953

    Article  CAS  PubMed  Google Scholar 

  20. Kassim SK, Ali HS, Sallam MM, Fayed ST, Seada LS, abd-Elkawy E, Seada MA, Khalifa A (1999) Increased bcl-2 expression is associated with primary resistance to chemotherapy in human epithelial ovarian cancer. Clin Biochem 32:333–338

    Article  CAS  PubMed  Google Scholar 

  21. Beale PJ, Rogers P, Boxall F, Sharp SY, Kelland LR (2000) BCL-2 family protein expression and platinum drug resistance in ovarian carcinoma. Br J Cancer 82:436–440

    Article  CAS  PubMed  Google Scholar 

  22. Altieri DC (2003) Survivin and apoptosis control. Adv Cancer Res 88:31–52

    CAS  PubMed  Google Scholar 

  23. Bhalla KN (2003) Microtubule-targeted anticancer agents and apoptosis. Oncogene 22:9075–9086

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Tania Dutta, Himani Sharma & Neeta Singh

  2. Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    A. K. Dinda

  3. Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Sunesh Kumar & Neerja Bhatla

  4. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Lalit Kumar

Authors
  1. Tania Dutta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Himani Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lalit Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. K. Dinda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sunesh Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Neerja Bhatla
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Neeta Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neeta Singh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dutta, T., Sharma, H., Kumar, L. et al. Neoadjuvant chemotherapy for epithelial ovarian cancer—role of apoptosis. Cancer Chemother Pharmacol 56, 427–435 (2005). https://doi.org/10.1007/s00280-004-0993-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-004-0993-9

Keywords

Search

Navigation