Antitumoral effect of PLK-1-inhibitor BI2536 in combination with cisplatin and docetaxel in squamous cell carcinoma cell lines of the head and neck

Wagenblast,Jens; Hirth,Daniel; Eckardt,Anne; Leinung,Martin; Diensthuber,Marc; Stöver,Timo; Hambek,Markus

doi:10.3892/mco.2012.45

Antitumoral effect of PLK-1-inhibitor BI2536 in combination with cisplatin and docetaxel in squamous cell carcinoma cell lines of the head and neck

Authors:
- Jens Wagenblast
- Daniel Hirth
- Anne Eckardt
- Martin Leinung
- Marc Diensthuber
- Timo Stöver
- Markus Hambek
View Affiliations

Affiliations: ENT Department, Medical School, Goethe University, D-60590 Frankfurt am Main, Germany
Published online on: November 27, 2012 https://doi.org/10.3892/mco.2012.45
Pages: 286-290

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

Inhibition of the polo-like-kinase-1 (PLK-1) has been shown to be effective in several haematological and solid tumor models. In this systemic in vitro study, the antitumor effect of BI2536, a small molecule inhibitor of PLK-1, in combination with cisplatin and docetaxel was examined in nine squamous cell carcinoma cell lines, most of which had a head and neck origin (SCCHN). Dose escalation studies were conducted with nine SCCHN cell lines using BI2536, cisplatin and docetaxel in cell line‑specific concentrations. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and a Human Apoptose Array kit. BI2536 in combination with cisplatin and docetaxel showed a markedly higher antiproliferative and apoptotic activity in the SCCHN cell lines investigated (P≤0.008), compared with single agent cisplatin or docetaxel alone. The findings of this study showed that the addition of PLK-1-inhibitor BI2536 to conventional chemotherapeutic drugs led to a statistically higher antiproliferative and apoptotic effect in SCCHN cell lines compared with cisplatin or docetaxel alone. Inaugurating BI2536 in the clinical setting might enhance the antitumoral activity of conventional drugs, possibly leading to less toxic side effects of cancer therapy.

View Figures

View References

1	Mehanna H, Paleri V, West CM and Nutting C: Head and neck cancer - Part 1: Epidemiology, presentation, and prevention. BMJ. 341:c46842010. View Article : Google Scholar : PubMed/NCBI
2	Wagenblast J, Hambek M, Baghi M, Gstöttner W, Strebhardt K, Ackermann H and Knecht R: Antiproliferative activity of bortezomib alone and in combination with cisplatin or docetaxel in head and neck squamous cell carcinoma cell lines. J Cancer Res Clin Oncol. 134:323–330. 2008. View Article : Google Scholar : PubMed/NCBI
3	Strebhardt K: Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat Rev Drug Discov. 9:643–660. 2010. View Article : Google Scholar : PubMed/NCBI
4	Barr FA, Sillje HH and Nigg EA: Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol. 5:429–440. 2004. View Article : Google Scholar : PubMed/NCBI
5	Andrysik Z, Bernstein WZ, Deng L, Myer DL, Li YQ, Tischfield JA, et al: The novel mouse Polo-like kinase 5 responds to DNA damage and localizes in the nucleolus. Nucleic Acids Res. 38:2931–2943. 2010. View Article : Google Scholar : PubMed/NCBI
6	Holtrich U, Wolf G, Bräuninger A, Karn T, Böhme B, Rübsamen-Waigmann H and Strebhardt K: Induction and down-regulation of PLK, a human serine/threonine kinase expressed in proliferating cells and tumors. Proc Natl Acad Sci USA. 91:1736–1740. 1994. View Article : Google Scholar : PubMed/NCBI
7	Lane HA and Nigg EA: Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J Cell Biol. 135:1701–1713. 1996. View Article : Google Scholar : PubMed/NCBI
8	Spankuch B, Steinhauser I, Wartlick H, Kurunci-Csacsko E, Strebhardt KI and Langer K: Downregulation of Plk1 expression by receptor-mediated uptake of antisense oligonucleotide-loaded nanoparticles. Neoplasia. 10:223–234. 2008.PubMed/NCBI
9	Van de Weerdt BC and Medema RH: Polo-like kinases: a team in control of the division. Cell Cycle. 5:853–864. 2006.PubMed/NCBI
10	Steegmaier M, Hoffmann M, Baum A, Lénárt P, Petronczki M, Krssák M, et al: BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Curr Biol. 17:316–322. 2007. View Article : Google Scholar : PubMed/NCBI
11	Takai N, Hamanaka R, Yoshimatsu J and Miyakawa I: Polo-like kinases (Plks) and cancer. Oncogene. 24:287–291. 2005. View Article : Google Scholar : PubMed/NCBI
12	Lénárt P, Petronczki M, Steegmaier M, Di Fiore B, Lipp JJ, Hoffmann M, et al: The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1. Curr Biol. 17:304–315. 2007.PubMed/NCBI
13	Wagenblast J, Hirth D, Thron L, Arnoldner C, Diensthuber M, Stöver T and Hambek M: Effects of the Polo-like-kinase-1-inhibitor BI2536 in squamous cell carcinoma cell lines of the head and neck. Oncol Lett. 4:175–177. 2012.PubMed/NCBI
14	Datta D, Banerjee P, Gasser M, Waaga-Gasser AM and Pal S: CXCR3-B can mediate growth-inhibitory signals in human renal cancer cells by down-regulating the expression of heme oxygenase-1. J Biol Chem. 285:36842–36848. 2010. View Article : Google Scholar : PubMed/NCBI
15	Ray RB, Raychoudhuri A, Steele R and Nerurkar P: Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis. Cancer Res. 70:1925–1931. 2010.PubMed/NCBI
16	Forastiere AA, Leong T, Rowinsky E, Murphy BA, Vlock DR, DeConti RC and Adams GL: Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393. J Clin Oncol. 19:1088–1095. 2001.
17	Schrijvers D, Johnson J, Jiminez U, Gore M, Kosmidis P, Szpirglas H, et al: Phase III trial of modulation of cisplatin/ fluorouracil chemotherapy by interferon alfa-2b in patients with recurrent or metastatic head and neck cancer. Head and Neck Interferon Cooperative Study Group. J Clin Oncol. 16:1054–1059. 1998.PubMed/NCBI
18	Kohno N: The role of taxanes for head and neck cancer. Gan To Kagaku Ryoho. 32:2035–2039. 2005.(In Japanese).
19	Jemal A, Siegel R, Ward E, Murray T, Xu J and Thun MJ: Cancer statistics. CA Cancer J Clin. 57:43–66. 2007.
20	Ackermann S, Goeser F, Schulte JH, Schramm A, Ehemann V, Hero B, et al: Polo-like kinase 1 is a therapeutic target in high-risk neuroblastoma. Clin Cancer Res. 17:731–741. 2011. View Article : Google Scholar : PubMed/NCBI
21	Hu K, Lee C, Qiu D, Fotovati A, Davies A, Abu-Ali S, et al: Small interfering RNA library screen of human kinases and phosphatases identifies polo-like kinase 1 as a promising new target for the treatment of pediatric rhabdomyosarcomas. Mol Cancer Ther. 8:3024–3035. 2009. View Article : Google Scholar : PubMed/NCBI
22	Chopra P, Sethi G, Dastidar SG and Ray A: Polo-like kinase inhibitors: an emerging opportunity for cancer therapeutics. Expert Opin Investig Drugs. 19:27–43. 2010. View Article : Google Scholar : PubMed/NCBI
23	Knecht R, Oberhauser C and Strebhardt K: PLK (polo-like kinase), a new prognostic marker for oropharyngeal carcinomas. Int J Cancer. 89:535–536. 2000. View Article : Google Scholar : PubMed/NCBI
24	Knecht R, Elez R, Oechler M, Solbach C, von Ilberg C and Strebhardt K: Prognostic significance of polo-like kinase (PLK) expression in squamous cell carcinomas of the head and neck. Cancer Res. 59:2794–2797. 1999.PubMed/NCBI
25	Mross K, Frost A, Steinbild S, Hedbom S, Rentschler J, Kaiser R, et al: Phase I dose escalation and pharmacokinetic study of BI 2536, a novel Polo-like kinase 1 inhibitor, in patients with advanced solid tumors. J Clin Oncol. 26:5511–5517. 2008. View Article : Google Scholar : PubMed/NCBI
26	Schöffski P, Blay JY, De Greve J, Brain E, Machiels JP, Soria JC, et al: Multicentric parallel phase II trial of the polo-like kinase 1 inhibitor BI 2536 in patients with advanced head and neck cancer, breast cancer, ovarian cancer, soft tissue sarcoma and melanoma. The first protocol of the European Organization for Research and Treatment of Cancer (EORTC) Network Of Core Institutes (NOCI). Eur J Cancer. 46:2206–2215. 2010.