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Published on: September 30, 2016
Anti-tumor effects of P-LPK-CPT, a peptide-camptothecin conjugate, in colorectal cancer
Lidan Hou1,2,3, Yichao Hou1,2,3, Yu Liang1,2,3
1Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
To explore highly selective targeting molecules of colorectal cancer (CRC) is a challenge. We previously identified a twelve-amino acid peptide (LPKTVSSDMSLN, namely P-LPK) by phage display technique which may specifically binds to CRC cells. Here we show that P-LPK selectively bind to a panel of human CRC cell lines and CRC tissues. In vivo, Gallium-68 (68Ga) labeled P-LPK exhibits selective accumulation at tumor sites. Then, we designed a peptide-conjugated drug comprising P-LPK and camptothecin (CPT) (namely P-LPK-CPT), and found P-LPK-CPT significantly inhibits tumor growth with fewer side effects in vitro and in vivo. Furthermore, through co-immunoprecipitation and molecular docking experiment, the glutamine transporter solute carrier 1 family member 5 (SLC1A5) was identified as the possible target of P-LPK. The binding ability of P-LPK and SLC1A5 is verified by surface plasmon resonance and immunofluorescence. Taken together, P-LPK-CPT is highly effective for CRC and deserves further development as a promising anti-tumor therapeutic for CRC, especially SLC1A5-high expression type.
Insights
A novel peptide, P-LPK, selectively targets colorectal cancer (CRC) cells and tissues. Conjugated with camptothecin (CPT) into P-LPK-CPT, it shows potent anti-tumor efficacy, particularly for SLC1A5-high CRC.
Area of Science:
- Oncology
- Molecular Biology
- Drug Development
Background:
- Developing highly selective targeting molecules for colorectal cancer (CRC) remains a significant challenge.
- Previous work identified a peptide (P-LPK) with potential specificity for CRC cells.
Purpose of the Study:
- To evaluate the targeting specificity and therapeutic potential of the P-LPK peptide in colorectal cancer.
- To investigate the efficacy of a peptide-conjugated drug (P-LPK-CPT) for CRC treatment.
Main Methods:
- Phage display technique for peptide identification.
- In vitro and in vivo studies using CRC cell lines and tissues.
- Radiolabeling with Gallium-68 (68Ga) for imaging.
- Co-immunoprecipitation, molecular docking, surface plasmon resonance, and immunofluorescence for target identification.
Main Results:
- P-LPK demonstrated selective binding to human CRC cell lines and tissues.
- 68Ga-labeled P-LPK showed selective accumulation at tumor sites in vivo.
- P-LPK-CPT significantly inhibited tumor growth with reduced side effects.
- Solute carrier 1 family member 5 (SLC1A5) was identified as the molecular target of P-LPK.
Conclusions:
- P-LPK-CPT is a highly effective therapeutic agent for colorectal cancer.
- The peptide P-LPK targets SLC1A5, a transporter upregulated in CRC.
- P-LPK-CPT shows promise for further development as an anti-CRC therapy, especially for SLC1A5-high expressing tumors.
