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A Novel CRAd in Combination With Cisplatin Enhanced the Antitumor Efficacy in Ovarian Cancer
  1. Bei Zhang, MD*,
  2. Yaowu Liu, PhD,,
  3. Peiying Zhang, MD*,
  4. Yaqin Wei, PhM,,
  5. Xiaoxing Yin, PhD, and
  6. Junnian Zheng, MD§
  1. * Department of Obstetrics and Gynecology, Xuzhou Central Hospital;
  2. Department of Clinical Pharmacology; and
  3. Key Laboratory of New Drugs and Clinical Application, and
  4. § Jiangsu Province Key Laboratory of Biological Therapy of Cancer, Xuzhou Medical College, Xuzhou, Jiangsu, China.
  1. Address correspondence and reprint requests to Bei Zhang, MD, Department of Obstetrics and Gynecology, Xuzhou Central Hospital 199, Southern Jiefang Rd, Xuzhou, Jiangsu 221009, China. E-mail: beizhangxz{at}gmail.com.

Abstract

Objectives The aim of this study was to investigate the combined effects of a novel survivin promoter-based conditionally replicating adenovirus (CRAd-S.RGD) plus cis-diamminedichloroplatinum (cisplatin, CDDP) in ovarian cancer in vitro and in vivo.

Methods The viability of human ovarian cancer cell line SKOV3 was determined by MTT assay following the infection with different doses of CRAd-S.RGD, either alone or in combination with CDDP. The antitumor efficacies and survival curves were evaluated at the end of the treatment regimens with the subcutaneous administration of CRAd-S.RGD, CDDP, combined therapy of CRAd-S.RGD plus CDDP, or phosphate-buffered saline in a SKOV3 xenograft animal model. Furthermore, the apoptosis rate of tumor tissues in mice was determined subsequent to the treatments.

Results In vitro, the CRAd-S.RGD destroyed SKOV3 cells by oncolysis in a dose-dependent manner, and the viability of SKOV3 cells was significantly lower in the combined-therapy group than that in the individual-therapy groups. In vivo, enhanced tumor inhibition and animal survival rates were obtained in a synergistic manner with CRAd-S.RGD plus CDDP, as compared with the treatment with CRAd-S.RGD or CDDP alone. There was an increase in the apoptosis rate of the cells following the combined therapy. The results clearly demonstrated that there was a synergistic effect in the combination of CRAd-S.RGD and CDDP in increased therapeutic efficacy. Similar therapeutic efficacy could be obtained with CRAd-S.RGD plus CDDP at 2 lower doses that minimized the drug toxicity to host tissues.

Conclusions The strategy of CRAd-S.RGD in combination with CDDP was a potential therapeutic modality for the therapy in ovarian cancer.

Abbreviations CDDP - cisplatin, cis-diamminedichloroplatinum, CRAd - conditionally replicating adenovirus, CRAd-survivin - the survivin promoter-based conditionally replicating adenovirus, CRAd-S.RGD - CRAd–survivin-RGD4C, MOI - multiplicity of infection, PBS - phosphate-buffered saline, PI - propidium iodide

  • CRAd
  • Cisplatin
  • Ovarian cancer
  • Synergism

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Footnotes

  • The authors have no conflicts of interest to declare.

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