title: CPP2-p16MIS treatment-induced colon carcinoma cell death in vitro and prolonged lifespan of tumor-bearing mice.
abstract: Cell-penetrating peptides (CPPs) are a research hotspot due to their noninvasive delivery ability. Among the identified CPPs, the TAT and R8 peptides have been preferentially applied to transduction into different cells. However, this process is nonselective among various cells. Recent research suggested that CPP2 could selectively penetrate human colorectal cancer (CRC) cells.
  
  
  
  Using in vitro experiments, the mean fluorescence intensity of fluorescein isothiocyanate-labeled CPPs (CPPs-FITC) incubated with different cell lines was compared to corroborate the colon tumor targeting ability of CPP2. The targeting ability of CPP2 was determined in the same way in tumor-bearing mice. We synthesized antitumor peptides by fusing CPP2 to the minimal inhibitory sequence of p16 (p16MIS), which had the ability to restore the function of lost p16, the expression of which was absent in tumor cell lines of various origins. The antitumor effect of the combined peptide was tested in both CRC cell lines and tumor-bearing mice.
  
  
  
  In each CRC cell line, the mean fluorescence intensity of CPP2-FITC was higher than that of the TAT-FITC (p < 0.001) and R8-FITC (p < 0.001) groups. CPP2-p16MIS, the targeting carrier, showed a higher antitumor response in the in vitro cell research. CPP2-p16MIS showed a prolonged mean lifespan of tumor-bearing mice, further characterizing its role in specific tumor-targeting ability in vivo. Survival analysis showed that the mice treated with CPP2-p16MIS had significantly longer survival than the mice treated with phosphate-buffered saline (p < 0.05) or those treated with control peptides, including the CPP2 (p < 0.05) and p16MIS (p < 0.05) groups.
  
  
  
  CPP2 could more selectively penetrate CRC cells than TAT or R8 as well as effectively deliver the p16MIS to the tumor.
authors.affiliation: Department of General Surgery, Zhu Jiang Hospital of Southern Medical University, Guang Zhou, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Zhu Jiang Hospital of Southern Medical University, Guang Zhou, China.
authors.forename: Haijin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Zhu Jiang Hospital of Southern Medical University, Guang Zhou, China. yujinlong640506@163.com.
authors.forename: Jinlong
authors.identifier: 0000-0002-4581-1726
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Zhu Jiang Hospital of Southern Medical University, Guang Zhou, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Zhu Jiang Hospital of Southern Medical University, Guang Zhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of General Surgery, Zhu Jiang Hospital of Southern Medical University, Guang Zhou, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of General Surgery, Zhu Jiang Hospital of Southern Medical University, Guang Zhou, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Ophthalmology, Zhu Jiang Hospital of Southern Medical University, Guang Zhou, China.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000628:therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000737:chemistry / Q000235:genetics*; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: C000614131:CDKN2A protein, human; D057846:Cell-Penetrating Peptides; D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: CPP2; Cell-penetrating peptides; Colon cancer; Molecular therapy; Targeting delivery