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Role of Survivin and p53 Expression in Response of Primary Culture of Ovarian Cancer Cells to Treatment With Chemotherapeutic Agents
  1. Diwesh Chawla, MSc*,
  2. Rajarshi Kar, MD,
  3. Bindiya Gupta, MD,
  4. Sumita Halder, MD, PhD§,
  5. Seema Garg, MD,
  6. Mohit Mehndiratta, MD,
  7. Neelam Wadhwa, MD and
  8. Rachna Agarwal, MD
  1. *Central Research Laboratory (Multi-disciplinary Research Unit),
  2. Department of Biochemistry,
  3. Department of Obstetrics and Gynecology,
  4. §Department of Pharmacology, and
  5. Department of Pathology, University College of Medical Sciences (University of Delhi), Dilshad Garden, Delhi, India.
  1. Address correspondence and reprint requests to Rajarshi Kar, MD, Department of Biochemistry, University College of Medical Sciences (University of Delhi); or Dilshad Garden, Delhi 110095, India. E-mail: rajarshi.kar@gmail.com.

Abstract

Background Ovarian cancer is associated with a high relapse rate and is the fifth leading cause of cancer deaths in women. The genetic profile of a tumor is responsible for deciding response to chemotherapeutic agents. In this study, we investigate the relation between survivin and p53 expression and response to chemotherapeutic agents of primary cultures of ovarian cancer cells established from ascitic fluid.

Materials and Method Ascitic fluid and Dulbecco’s modified Eagle medium was mixed in equal proportion in culture flasks and incubated to establish primary culture. The cells were treated with different combinations of carboplatin and paclitaxel with and without survivin small interfering RNA transfection. Cell survival was estimated by MTT assay. Survivin and p53 expression was quantified by real-time polymerase chain reaction.

Results Out of 19 ascitic fluid samples, 13 primary cultures of ovarian cancer cells were established. The half maximal inhibitory concentration doses of carboplatin (≥70 μg/mL) and paclitaxel (≥18 μg/mL) were high for 10/13 and 5/13 patients, respectively. Survivin messenger RNA expression was significantly downregulated on treatment with carboplatin (100 μg/mL), paclitaxel (12.5 μg/mL), and a combination of carboplatin (50 μg/mL) and paclitaxel (6.25 μg/mL). Only paclitaxel-treated ovarian cancer cells showed decrease in expression of p53. Survivin small interfering RNA increased sensitivity of the primary cultures to chemotherapeutic agents.

Conclusions The present study highlights the fact that establishing primary cultures from ascitic fluid may help to develop personalized treatment regime for individual patients based on their molecular profile. Our study also shows that supplementing taxols drugs with survivin inhibitors may prove to be beneficial in the treatment of ovarian cancer patients.

  • Ovarian cancer
  • survivin
  • p53 expression
  • chemotherapy

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Footnotes

  • The authors declare no conflict of interest.

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