Abstract
Background and ObjectiveOur previous study showed that liver graft injury not only promotes tumor recurrence, but also induces chemoresistance in recurrent HCC after liver transplantation. Recently, we found that the hemoglobin-based oxygen carrier“YQ23” significantly ameliorates hepatic IR injury and prevent tumor recurrence. Here, we intended to explore the novel therapeutic strategy using oxygen carrier “YQ23”to sensitize chemotherapy in HCC.MethodsTo investigate the role of YQ23 combined with Cisplatin, the proliferation of HCC cells was examined under combined treatment by MTT and colony formation. To explore the effect of YQ23 on sensitization of Cisplatin based chemotherapy, the orthotopic liver cancer model was established. To characterize the delivery of YQ23 in tumor tissue, the intravital imaging system was applied for longitudinal observation in ectopic liver cancer model. The distribution of YQ23 was examined by IVIS spectrum.ResultsYQ23 significantly suppressed the proliferation of HCC cells under Cisplatin treatment in a dose and time dependent manner. Moreover, YQ23 administration significantly sensitized Cisplatin based chemotherapy in orthotopic liver cancer model. Down-regulation of DHFR may be one of the reasons for YQ23 sensitizing Cisplatin based chemotherapy. Real-time intravital imaging showed that YQ23 accumulated in the tumor tissue and maintained as long as 3 days in ectopic liver cancer model. The IVIS spectrum examination showed that YQ23 distributed mainly at liver and bladder within the first 36 hours after administration in orthotopic liver cancer model.ConclusionYQ23 treatment may be a potential therapeutic strategy to sensitize chemotherapy in HCC.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common cancer and ranks as high as third for cancerrelated deaths worldwide [1]
YQ23 significantly suppressed the proliferation of HCC cells under Cisplatin treatment in a dose and time dependent manner
Real-time intravital imaging showed that YQ23 accumulated in the tumor tissue and maintained as long as 3 days in ectopic liver cancer model
Summary
Hepatocellular carcinoma (HCC) is the sixth most common cancer and ranks as high as third for cancerrelated deaths worldwide [1]. Our previous study showed that severe hepatic ischemiareperfusion (IR) injury promotes tumor recurrence, and induces chemoresistance in recurrent HCC after liver transplantation [2]. Recent reports showed that Egr-1 (Early growth response protein 1) promotes chemoresistance in HCC through hypoxia induced autophagy [10]. As hypoxia is inevitable in liver transplantation and hypoxia induced chemoresistance could occur in recurrent HCC posttransplantation [2], attenuation of hypoxia environment of tumor cells using oxygen carrier may provide new insight for developing therapeutic strategy targeting at chemoresistance in HCC, especially for recurrent HCC after liver transplantation. Our previous study showed that liver graft injury promotes tumor recurrence, and induces chemoresistance in recurrent HCC after liver transplantation. We intended to explore the novel therapeutic strategy using oxygen carrier “YQ23”to sensitize chemotherapy in HCC
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