1. Department of Genetics and Cell Biology, Basic medical school, 308 Ningxia Road, Qingdao University, Qingdao, China, 266071.
2. The Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, FL, USA.
* Liangqian Jiang and Yujuan Wang contributed equally to this article.
The novel tumor targeted nano-drug C-PC/CMC-CD59sp nanoparticles were constructed with carbocymethyl chitosan (CMC), C-phycocyanin (C-PC) and CD59 specific ligand peptide (CD59sp). The anti-tumor drug mechanism of the C-PC/CMC-CD59sp NPs was further explored in cervical cancer cells (HeLa and SiHa) in vitro and in vivo. We found that the C-PC/CMC-CD59sp NPs could inhibit the proliferation and induce G0/G1 cell cycle arrest in cervical cancer HeLa and SiHa cells, and the cell proliferation was reduced in a dose-dependent manner. We further found that the C-PC/CMC-CD59sp NPs regulated the cell cycle via up-regulating the expression of p21, and then down-regulating the expressions of Cyclin D1 and CDK4 in vivo. Compared with C-PC and C-PC/CMC NPs, the pro-apoptosis effects of the C-PC/CMC-CD59sp NPs were more significant for HeLa and SiHa cells in vitro. Moreover, the C-PC/CMC-CD59sp NPs up-regulated the expression of cleaved caspase-3 and down-regulated the expression of bcl-2. In addition, compared with C-PC and C-PC/CMC, the C-PC/CMC-CD59sp NPs significantly inhibited MMP-2 protein expression in vivo. Our data suggested that the anti-tumor effects of C-PC/CMC-CD59sp NPs were better than C-PC and C-PC/CMC NPs. Our laboratory constructed a new drug delivery system and proved the effective antitumor effects of C-PC/CMC-CD59sp, which would widen the application of C-PC as a potential anti cervical cancer drug.
Keywords: C-PC/CMC-CD59sp, cell cycle arrest, apoptosis, Bcl-2/Cleaved caspase-3, cervical cancer