Targeting PEPT1: a novel strategy to improve the antitumor efficacy of doxorubicin in human hepatocellular carcinoma therapy
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Yanxia Gong1,2, Xiang Wu3, Tao Wang1, Jia Zhao3, Xi Liu1, Zhi Yao4, Qingyu Zhang1 and Xu Jian3
1Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, 300052, China
2Department of Gastroenterology, Tianjin Nankai Hospital, Tianjin, 300100, China
3Central Laboratory, Tianjin Medical University General Hospital, Tianjin, 300052, China
4Department of Immunology, School of Basic Medical Science, Tianjin Medical University, Tianjin, 300070, China
Xu Jian, email: [email protected]
Qingyu Zhang, email: [email protected]
Keywords: proton coupled oligopeptide transporter 1, doxorubicin, hepatocellular carcinoma (HCC), target therapy, toxicity
Received: September 02, 2016 Accepted: April 02, 2017 Published: April 15, 2017
Proton coupled oligopeptide transporter 1 (PEPT1) is a member of the peptide transporter superfamily and plays important role in the absorption of oligopeptide and peptidomimetic drugs. Our previous research verified that PEPT1 expressed specifically in human Hepatocellular carcinoma (HCC) tissue and cell lines and showed potential transport activity to be a new candidate of the tumor therapeutic target. In this study, we aim to explore the feasibility of a novel tumor target therapeutic strategy: Targeting PEPT1 to improve the antitumor efficacy of Doxorubicin in human HCC therapy. First, Doxorubicin was conjugated with Glycylglycylglycine (Gly-Gly-Gly) − a tripeptide which was known as the substrate of PEPT1 and characterized by HPLC and MS successfully. Doxorubicin-tripeptide conjugate was then observed to clarify the target delivery by PEPT1 and the antitumor effect on human hepatocarcinoma in vivo and in vitro. Furthermore, the improvement of the toxic and side effect of Doxorubicin after conjugation was also evaluated by some biochemical tests. Our results reveal that targeting PEPT1 may contribute to the efficient delivery of Doxorubicin to hepatocarcinoma cells and the reduction of drug toxicity. PEPT1 has the prospect to be a novel target of HCC therapy.
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