title: Dual-modality imaging demonstrates the enhanced antitumoral effect of herpes simplex virus-thymidine kinase/ganciclovir plus gemcitabine combination therapy on cholangiocarcinoma.
abstract: Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) therapy is one of the most promising therapeutic strategies for the treatment of cholangiocarcinoma, which is the second most common hepatobiliary cancer. The aim of the present study was to evaluate the enhanced therapeutic effects of HSV-TK/GCV with gemcitabine on cholangiocarcinoma. QBC939 cholangiocarcinoma cells and mouse models of cholangiocarcinoma (established via tumor xenografts) received one of the following treatments: i) Gemcitabine therapy (3 µg/ml); ii) HSV-TK/GCV monotherapy; iii) HSV-TK/GCV + gemcitabine; and iv) control group, treated with phosphate-buffered saline. Cell proliferation was quantified using MTT assay and post-treatment tumor alterations were monitored using ultrasound imaging and optical imaging. For thein vitroexperiments, the MTT assays demonstrated that the relative cell viabilities in the gene therapy, gemcitabine and gemcitabine + gene groups were 70.37±9.07, 52.64±8.28 and 34.21±6.63%, respectively. For thein vivoexperiments, optical imaging indicated significantly decreased optical signals in the combination therapy group, as compared with the gemcitabine and gemcitabine + gene groups (1.68±0.74 vs. 2.27±0.58 and 2.87±0.82, respectively; Р<0.05). As demonstrated by ultrasound imaging, reduced tumor volumes were detected in the combination therapy group, as compared with the three control groups (114.32±17.17 vs. 159±23.74, 201.63±19.26 and 298.23±36.1 mm3, respectively; P<0.05). The results of the present study demonstrated that gemcitabine enhances the antitumoral effects of HSV-TK/GCV on cholangiocarcinoma, which may provide a novel therapeutic strategy for the management and treatment of cholangiocarcinoma using gemcitabine and gene therapy.
authors.affiliation: Department of Interventional Radiology, Beijing Chaoyang Hospital, Beijing 100020, P.R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, Public Health School, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Radiology, First Hospital of Qiqihar, Qiqihar, Heilongjiang 161006, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Jin
authors.affiliation: Department of Radiology, First Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Radiology, First Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
keywords: cholangiocarcinoma; gemcitabine; herpes simplex virus-thymidine kinase/ganciclovir; optical imaging