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Treatment of Human Thyroid Carcinoma Cells with the G47delta Oncolytic Herpes Simplex Virus

  • Wang, Jia-Ni (Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University) ;
  • Xu, Li-Hua (Department of Oncology and Hematology, The First Affiliated Hospital of Guangzhou Medical University) ;
  • Zeng, Wei-Gen (Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University) ;
  • Hu, Pan (Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University) ;
  • Rabkin, Samuel D. (Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School) ;
  • Liu, Ren-Rin (Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University)
  • Published : 2015.03.04

Abstract

Background: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, $G47{\Delta}$, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of $G47{\Delta}$. Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with $G47{\Delta}$ at different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either $G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results: $G47{\Delta}$ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to $G47{\Delta}$, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to $G47{\Delta}$; $G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV $G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro. $G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, $G47{\Delta}$ may hold great promise for thyroid cancer patients.

Keywords

Thyroid carcinoma;oncolytic herpes simplex virus;cytotoxicity;subcutaneous models

Acknowledgement

Supported by : National Natural Science Foundation

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