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

  • Commun Biol. 2022 Nov 14;5(1):1248. doi: 10.1038/s42003-022-04191-1.
Lidan Hou  #  1  2  3 ,  Yichao Hou  #  1  2  3 ,  Yu Liang  #  1  2  3 ,  Baiyu Chen  4 ,  Xintian Zhang  1  2  3 ,  Yu Wang  1  2  3 ,  Kun Zhou  1  2  3 ,  Ting Zhong  1  2  3 ,  Bohan Long  1  2  3 ,  Wenjing Pang  1  2  3 ,  Lei Wang  1  2  3 ,  Xu Han  1  2  3 ,  Linjing Li  1  2  3 ,  Ci Xu  1  2  3 ,  Isabelle Gross  5  6 ,  Christian Gaiddon  5  6 ,  Wei Fu  7 ,  Han Yao  8  9  10 ,  Xiangjun Meng  11  12  13
Affiliations
  • 1. Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2. Center for Digestive Diseases Research and Clinical Translation of Shanghai Jiao Tong University, Shanghai, China.
  • 3. Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Shanghai, China.
  • 4. Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, China.
  • 5. INSERM UMR_S1113, IRFAC, Strasbourg, F-67200, France.
  • 6. Universite de Strasbourg, Strasbourg, 67200, France.
  • 7. Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, China. [email protected].
  • 8. Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 9. Center for Digestive Diseases Research and Clinical Translation of Shanghai Jiao Tong University, Shanghai, China. [email protected].
  • 10. Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Shanghai, China. [email protected].
  • 11. Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 12. Center for Digestive Diseases Research and Clinical Translation of Shanghai Jiao Tong University, Shanghai, China. [email protected].
  • 13. Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 36376440 DOI: 10.1038/s42003-022-04191-1
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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