Anti-tumor effects of P-LPK-CPT, a peptide-camptothecin conjugate, in colorectal cancer

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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.

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Hou, L., Hou, Y., Liang, Y., Chen, B., Zhang, X., Wang, Y., … Meng, X. (2022). Anti-tumor effects of P-LPK-CPT, a peptide-camptothecin conjugate, in colorectal cancer. Communications Biology, 5(1). https://doi.org/10.1038/s42003-022-04191-1

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