Antitumor Efficacy of Docetaxel-loaded Nanocarrier against Esophageal Cancer Cell Bearing Mice Model

Z.-J. Huang; N. Yang; T.-W. Xu; J.-Q. Lin

doi:10.1055/s-0034-1385907

Drug Research, Table of Contents

Drug Res (Stuttg) 2015; 65(08): 403-409
DOI: 10.1055/s-0034-1385907

Original Article

Antitumor Efficacy of Docetaxel-loaded Nanocarrier against Esophageal Cancer Cell Bearing Mice Model

Z.-J. Huang

¹Department of Oncology, The Second Affiliated Hospital of Fujian Medical University, Fujian, China

,

N. Yang

²Obstetrics and Gynecology Department, The Second Affiliated Hospital of Fujian Medical University, Fujian, China

,

T.-W. Xu

¹Department of Oncology, The Second Affiliated Hospital of Fujian Medical University, Fujian, China

,

J.-Q. Lin

¹Department of Oncology, The Second Affiliated Hospital of Fujian Medical University, Fujian, China

› Author Affiliations

Abstract

Esophageal carcinoma is one of the most prevalent cancers with high rate of mortality worldwide. Intravenous and oral-based chemotherapeutic regimens were employed; however all the current treatment modalities are largely unsuccessful. Therefore the main aim of this work was to demonstrate the antitumor efficacy of docetaxel (DTX)-loaded trimethyl chitosan (TMC-DTX) against EC9701 esophageal squamous cancer cells. We showed a superior anti-proliferative activity for TMC-DTX against EC9701 cells upon incubation for 24, 48, and 72 h. Notably, nanoparticles effectively killed the cancer cells at longer incubation time which was consistent with the fact that much of the cells enter G2 and M phase at longer incubation at which DTX is most effective. Furthermore, Annexin V/PI based cell apoptosis study further confirmed the enhanced anticancer activity of DTX formulations. Cell-cycle analysis showed a substantial proportion of cells in subG₀ and G2/M phase of cell arrest. Importantly, TMC-DTX showed a remarkable tumor regression profile in EC9701 tumor bearing mice. The intravenous administration significantly controlled/delayed the growth of tumor by comparison to free drug. Therefore TMC-DTX could a potential drug delivery system to enhance the chemotherapeutic efficacy in esophageal carcinoma.

Key words

esophageal cancer - docetaxel - anticancer activity - chemotherapy

Full Text

References

References
1 Ahmedin J, Freddie B, Melissa M et al. Global cancer statistics. Ca Cancer J Clin 2011; 61: 69-75
2 Shahbaz Sarwar CM, Luketich JD, Landreneau RJ et al. Esophageal cancer: an update. Int J Surg 2010; 8: 417-422
3 Jemal A, Siegel R, Ward E et al. Cancer statistics. CA Cancer J Clin 2009; 59: 225-249
4 Zheng RS, Zhang SW, WU LY et al. Report of incidence and mortality from China Cancer Registries in 2008. China Cancer 2012; 21: 1-8
5 Liu Q, Li R, Zhu Z et al. Enhanced antitumor efficacy, biodistribution and penetration of docetaxel-loaded biodegradable nanoparticles. Int J Pharm 2012; 430: 350-358
6 Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 2005; 5: 161-171
7 De Britto D, Assis OBG. A novel method for obtaining a quaternary salt of chitosan. Carb Polym 2007; 69: 305-310
8 Slütter B, Jiskoot W. Dual role of CpG as immune modulator and physical crosslinker in ovalbumin loaded N-trimethyl chitosan (TMC) nanoparticles for nasal vaccination. J Control Rel 2010; 148: 117-121
9 Hamman JH, Stander M, Kotze AF. Effect of the degree of quaternisation of N-trimethyl chitosan chloride on absorption enhancement: In vivo evaluation in rat nasal epithelia. Int J Pharm 2002; 232: 235-242
10 Capri G, Tarenzi E, Fulfaro F et al. The role of taxanes in the treatment of breast cancer. Exp Opin Pharmacother 2005; 6: 1073-1094
11 Gueritte-Voegelein F, Guenard D, Lavelle F et al. Relationships between the structure of taxol analogs and their antimitotic activity. J Med Chem 1991; 34: 992-998
12 Yan YD, Kim DH, Sung JH et al. Enhanced oral bioavailability of docetaxel in rats by four consecutive days of pre-treatment with curcumin. Int J Pharm 2010; 399: 116-120
13 De Britto D, Forato LA, Assis OBG. Determination of the average degree of quaternization of N, N, N-trimethylchitosan by solid state C-13 NMR. Carb Polym 2008; 74: 86-91
14 Bhumkar DR, Pokharkar VB. Studies on effect of pH on cross-linking of chitosan with sodium tripolyphosphate: a technical note. AAPS PharmSciTech 2006; 7
15 Chen F, Zhang ZR, Huang Y. Evaluation and modification of N-trimethyl chitosan chloride nanoparticles as protein carriers. Int J Pharm 2007; 336: 166-173
16 Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 1989; 49: 6449-6465
17 Sauvant C, Nowak M, Wirth C et al. Acidosis induces multi-drug resistance in rat prostate cancer cells (AT1) in vitro and in vivo by increasing the activity of the p-glycoprotein via activation of p38. Int J Cancer 2008; 123: 2532-2542
18 Jordan MA, Toso RJ, Thrower D et al. Mechanism of mitotic block and inhibition of cell proliferation by Taxol at low concentrations. Proc Natl Acad Sci USA 1993; 90: 9552-9556
19 Feng SS, Mei L, Anitha P et al. Poly(lactide)-vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of Docetaxel. Biomaterials 2009; 30: 3297-3306
20 Minko T, Batrakova EV, Li S et al. Pluronic block copolymers alter apoptotic signal transduction of doxorubicin in drug-resistant cancer cells. J Control Release 2005; 105: 269-278
21 Ng SSW, Tsao MS, Chow S et al. Inhibition of phosphatidylinositide 3-kinase enhances gemcitabine-induced apoptosis in human pancreatic cancer cells. Cancer Res 2008; 60: 5451-5455
22 Liu Z, Chen K, Davis C et al. Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer Res 2008; 68: 6652-6660