A novel therapy for ovarian cancer using real‑time imaging

Zhang,Zhen; Chen,Zhaojie; Xie,Beibei; Zhang,Haiyan

doi:10.3892/mmr.2016.6000

A novel therapy for ovarian cancer using real‑time imaging

Authors:
- Zhen Zhang
- Zhaojie Chen
- Beibei Xie
- Haiyan Zhang
View Affiliations

Affiliations: Department of Gynaecology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
Published online on: December 7, 2016 https://doi.org/10.3892/mmr.2016.6000
Pages: 291-296

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study was designed to develop an activable, dual‑targeted theranostic platform combining fluorescent and cytotoxic templates to provide a novel strategy for specific drug delivery and cellular imaging in ovarian cancer cells. Two compounds of a folic acid‑prodrug‑doxorubicin (Dox) scaffold were synthesized, and their antiproliferative activities were evaluated using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide and flow cytometric analysis. The process of drug release was investigated using fluorescence emission spectra assay and confocal laser scanning microscopy. The results showed that the synthesized compounds exhibited potent antitumor activities against ovarian cell lines. Among them, compound 1e exhibited the most potent activity demonstrating half maximal inhibitory concentration values of 0.85±0.10, 8.64±0.37 and 0.81±0.03 µM against A2780, A2780/Dox and A2780/cisplatin cell lines. The fluorescence imaging of live cell lines also provided an easy and reliable method to monitor site‑specific drug activities through turn‑on systems induced by drug release. The results of the present study may assist in the treatment of ovarian cancer cells with strengthened efficiency and real‑time imaging, which may be used as a multifunctional system for the optimization of anticancer drugs.

View Figures

View References

1	Mareel M and Leroy A: Clinical, cellular, and molecular aspects of cancer invasion. Physiol Rev. 83:337–376. 2003. View Article : Google Scholar : PubMed/NCBI
2	Weigelt B, Peterse JL and Van't Veer LJ: Breast cancer metastasis: Markers and models. Nat Rev Cancer. 5:591–602. 2005. View Article : Google Scholar : PubMed/NCBI
3	Oldenburg RA, Meijers-Heijboer H, Cornelisse CJ and Devilee P: Genetic susceptibility for breast cancer: How many more genes to be found? Crit Rev Oncol Hematol. 63:125–149. 2007. View Article : Google Scholar : PubMed/NCBI
4	Nowsheen S, Aziz K, Tran PT, Gorgoulis VG, Yang ES and Georgakilas AG: Epigenetic inactivation of DNA repair in breast cancer. Cancer Lett. 342:213–222. 2014. View Article : Google Scholar : PubMed/NCBI
5	Leber MF and Efferth T: Molecular principles of cancer invasion and metastasis (review). Int J Oncol. 34:881–895. 2009.PubMed/NCBI
6	Yoo HS and Park TG: Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA-PEG block copolymer. J Control Release. 70:63–70. 2001. View Article : Google Scholar : PubMed/NCBI
7	Low PS and Antony AC: Folate receptor-targeted drugs for cancer and inflammatory diseases. Adv Drug Deliv Rev. 56:1055–1058. 2004. View Article : Google Scholar : PubMed/NCBI
8	Lu Y, Sega E, Leamon CP and Low PS: Folate receptor-targeted immunotherapy of cancer: Mechanism and therapeutic potential. Adv Drug Deliv Rev. 56:1161–1176. 2004. View Article : Google Scholar : PubMed/NCBI
9	Hilgenbrink AR and Low PS: Folate receptor-mediated drug targeting: From therapeutics to diagnostics. J Pharm Sci. 94:2135–2146. 2005. View Article : Google Scholar : PubMed/NCBI
10	Santra S, Kaittanis C, Santiesteban OJ and Perez JM: Cell-specific, activatable, and theranostic prodrug for dual-targeted cancer imaging and therapy. J Am Chem Soc. 133:16680–16688. 2011. View Article : Google Scholar : PubMed/NCBI
11	Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK and Wood WC: Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: An intergroup trial (E1193). J Clin Oncol. 21:588–592. 2003. View Article : Google Scholar : PubMed/NCBI
12	Heister E, Neves V, Silva SRP, Mcfadden J and Coley HM: Carbon nanotubes loaded with anticancer drugs: A platform for multimodal cancer treatmentCarbon Nanotubes for Biomedical Applications. Klingeler R and Sim RB: Springer-Verlag GmbH; Berlin: pp. 223–245. 2009
13	Karukstis KK, Thompson EH, Whiles JA and Rosenfeld RJ: Deciphering the fluorescence signature of daunomycin and doxorubicin. Biophys Chem. 73:249–263. 1998. View Article : Google Scholar : PubMed/NCBI
14	Jakupec MA, Galanski M and Keppler BK: Tumor-inhibiting platinum complexes-state of the art and future perspectives. Rev Physiol Biochem Pharmacol. 146:1–54. 2003. View Article : Google Scholar : PubMed/NCBI
15	Hall MD, Mellor HR, Callaghan R and Hambley TW: Basis for design and development of platinum (IV) anticancer complex. J Med Chem. 50:3403–3411. 2007. View Article : Google Scholar : PubMed/NCBI
16	Tyagi AK, Agarwal C, Chan DC and Agarwal R: Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Oncol Rep. 11:493–499. 2014.
17	Chun R, Kurzman ID, Couto CG, Klausner J, Henry C and MacEwen EG: Cisplatin and doxorubicin combination chemotherapy for the treatment of canine osteosarcoma: A pilot study. J Vet Intern Med. 14:495–498. 2000. View Article : Google Scholar : PubMed/NCBI
18	Harrington KJ, Syrigos KN, Uster PS, Zetter A, Lewanski CR, Gullick WJ, Vile RG and Stewart JS: Targeted radiosensitisation by pegylated liposome-encapsulated 3′, 5′-O-dipalmitoyl 5-iodo-2′-deoxyuridine in a head and neck cancer xenograft model. Br J Cancer. 91:366–373. 2004.PubMed/NCBI