Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide
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
Our study reveals that the protein and mRNA expression of PEPT1 were higher in HCC cells Bel-7402 and HepG2, as well as in Caco-2 cells, compared with normal liver cell line HL-7702, according to Western blotting and real-time RT-PCR (Figure 1A and 1B)
Summary
HCC is one of the most common malignant tumors worldwide. China has the high morbidity and mortality of HCC and the number of the HCC patients in China account for 54% of the world [1]. Due to the occult onset and difficult to early diagnosis, most of the HCC patients missed the optimal operating timing. Non-operative therapy including chemotherapy is an important treatment strategy for advanced HCC. Doxorubicin is a traditional chemotherapeutic agent for a wide variety of cancers. Despite of being highly effective, the use of Doxorubicin has many limitations due to the significant toxicity and side effects occurred during and after HCC treatment. These toxicities usually affect heart, brain, bone marrow and the consequences of these toxicities are often very apparent and will lasted for many years after treatment [2]. It is urgent to explore the new therapeutic strategy to improve the efficacy of the antitumor agents
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
