2. Academic Validation
  3. Anti-tumor effects of P-LPK-CPT, a peptide-camptothecin conjugate, in colorectal cancer

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

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. wfu@fudan.edu.cn.
  • 8 Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. hanyao89@163.com.
  • 9 Center for Digestive Diseases Research and Clinical Translation of Shanghai Jiao Tong University, Shanghai, China. hanyao89@163.com.
  • 10 Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Shanghai, China. hanyao89@163.com.
  • 11 Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. meng_xiangjun@yahoo.com.
  • 12 Center for Digestive Diseases Research and Clinical Translation of Shanghai Jiao Tong University, Shanghai, China. meng_xiangjun@yahoo.com.
  • 13 Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Shanghai, China. meng_xiangjun@yahoo.com.
  • # 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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