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BMC Cancer

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Open Access 01-12-2016 | Research article

CPP2-p16MIS treatment–induced colon carcinoma cell death in vitro and prolonged lifespan of tumor-bearing mice

Authors: Lifeng Wang, Haijin Chen, Jinlong Yu, Xiaohua Lin, Jia Qi, Chunhui Cui, Lang Xie, Shuxin Huang

Published in: BMC Cancer | Issue 1/2016

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

CPP2 could more selectively penetrate CRC cells than TAT or R8 as well as effectively deliver the p16MIS to the tumor.

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Title: CPP2-p16MIS treatment–induced colon carcinoma cell death in vitro and prolonged lifespan of tumor-bearing mice
Authors: Lifeng Wang
Haijin Chen
Jinlong Yu
Xiaohua Lin
Jia Qi
Chunhui Cui
Lang Xie
Shuxin Huang
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-016-2498-4

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