Abstract
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, G47Δ, 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 G47Δ. The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with G47Δat 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 G47Δor mock. Tumor volumes and mouse survival times were documented. G47Δ 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 G47Δ, 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 G47Δ G47Δ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. The oHSV G47Δ can effectively kill different types of human thyroid carcinomas in vitro. G47Δ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, G47Δ may hold great promise for thyroid cancer patients.
Highlights
Thyroid carcinoma, which consists of a group of diseases with different clinicopathologic features, is the most common malignancy of the endocrine organs (Vanderpump, 2011)
We investigated the therapeutic effects of a third-generation HSV vector, G47Δ, on various human thyroid carcinoma cell lines in vitro
In vitro cytotoxicity To assess the susceptibility of human thyroid carcinoma cell lines to G47Δ, various thyroid carcinoma cells were infected with G47Δ at a low multiplicities of infection (MOI) (MOI 0.01 and 0.1)
Summary
Thyroid carcinoma, which consists of a group of diseases with different clinicopathologic features, is the most common malignancy of the endocrine organs (Vanderpump, 2011). ATC is one of the most aggressive tumor types, with a median survival time of no more than 6 months (Are and Shaha, 2006; Lin et al, 2008; Smallridge et al, 2012). Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with G47Δ at different multiplicities of infection (MOIs) in vitro. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to G47Δ; G47Δ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV G47Δ can effectively kill different types of human thyroid carcinomas in vitro. G47Δ may hold great promise for thyroid cancer patients
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