Antiproliferative activity of bortezomib alone and in combination with cisplatin or docetaxel in head and neck squamous cell carcinoma cell lines.
OBJECTIVE
Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, we investigated the antitumor effect of bortezomib (Velcade((R))) in squamous cell carcinoma of the head and neck (SCCHN) cell lines and examined the interaction of the drug with docetaxel (TAX) and cisplatin (CDDP).


METHODS
Dose escalation studies were performed with eight squamous cell carcinoma cell lines using bortezomib alone or in combination with TAX or CDDP. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and western blot analysis.


RESULTS
Bortezomib alone showed a significant antiproliferative activity in all SCCHN cell lines (P = 0.012), and the activity was further enhanced by the addition of TAX or CDDP (P </= 0.036). When the combination of bortezomib and CDDP was used, the dose of the latter could be reduced to yield the same antiproliferative effect as the cytotoxic drug alone (P < 0.012).


CONCLUSIONS
Our results indicate that bortezomib increases the cytotoxic activity of TAX and CDDP in SCCHN cell lines. In vivo and in the clinical setting, the addition of bortezomib may allow to reduce the doses of TAX or CDDP to decrease the systemic toxicity of these drugs.
Wagenblast
Jens
J
ENT Department, Medical School, Goethe University, Frankfurt am Main, Germany.
Hambek
Markus
M
Baghi
Mehran
M
Gstöttner
Wolfgang
W
Strebhardt
Klaus
K
Ackermann
Hanns
H
Knecht
Rainald
R
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D001897:Boronic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D000069286:Bortezomib; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D043823:Taxoids; D000077143:Docetaxel; D000069286:Bortezomib; D002945:Cisplatin
Mol Cancer Ther. 2004 Jan;3(1):59-70
14749476
Epidemiol Prev. 2004 Mar-Apr;28(2 Suppl):28-33
15281603
Mol Cell Biol. 2004 Nov;24(22):9695-704
15509775
Asian Pac J Cancer Prev. 2006 Apr-Jun;7(2):195-200
16839210
Gan To Kagaku Ryoho. 2005 Dec;32(13):2035-9
16352925
Mol Cancer Ther. 2002 Aug;1(10):841-9
12492117
Curr Pharm Biotechnol. 2006 Dec;7(6):441-8
17168660
Clin Cancer Res. 2003 Oct 1;9(12):4537-45
14555528
Cancer Sci. 2004 Feb;95(2):176-80
14965369
J Clin Oncol. 2006 Nov 1;24(31):5025-33
17075122
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2727-30
9501156
J Clin Oncol. 1992 Feb;10(2):257-63
1732427
Anticancer Agents Med Chem. 2007 May;7(3):359-65
17504161
Nat Rev Cancer. 2004 May;4(5):349-60
15122206
Clin Lung Cancer. 2004 Dec;6 Suppl 2:S89-96
15638966
J Biol Chem. 2006 Oct 20;281(42):31440-7
16928686
Clin Cancer Res. 2003 Mar;9(3):1145-54
12631620
Anticancer Res. 1998 Nov-Dec;18(6B):4779-86
9891557
Cancer Treat Rev. 2003 May;29 Suppl 1:41-8
12738242
Cancer Chemother Pharmacol. 2004 Oct;54(4):343-53
15197486
Cancer Treat Rev. 2003 May;29 Suppl 1:21-31
12738240
J Clin Oncol. 1992 Aug;10(8):1245-51
1634913
Eur J Cancer. 2004 Oct;40(15):2217-29
15454246
Ann Oncol. 1994 Jul;5(6):521-6
7522527
J Clin Oncol. 1998 Mar;16(3):1054-9
9508190
J Clin Oncol. 2001 Feb 15;19(4):1088-95
11181673
Clin Cancer Res. 2006 Feb 15;12(4):1270-5
16489083