Enhanced anticancer effect of the combination of cisplatin and TRAIL in triple-negative breast tumor cells.
Women with triple-negative breast cancer (TNBC) have a worse prognosis compared with other breast cancer subtypes. Hormonal or Herceptin-based therapies were found to be ineffective because of the loss of target receptors, such as ER, PR, and HER-2 amplification. Conventional chemo- and/ or radiation therapy also seems to have limited efficacy in TNBC patients. We studied the effects of cisplatin plus TRAIL on 1 normal and 2 TNBC cells in vitro. The in vitro studies indicate that cisplatin plus TRAIL significantly enhanced cell death in TNBC cell lines CRL2335 and MDA-MB-468 by approximately 60%-70% compared with approximately 10%-15% in CRL8799 normal breast cell line. Treatment with cisplatin/TRAIL also inhibited the expression of EGFR, p63, survivin, Bcl-2, and Bcl-xL in TNBC cells. Specific inhibition of EGFR and/or p63 protein in TNBC cells by small interfering RNA (siRNA) does not increase TRAIL-induced apoptosis. However, inhibition of survivin by siRNA enhances TRAIL-induced apoptosis. These observations suggested the possibility that survivin played an important role in cisplatin plus TRAIL-induced apoptosis in TNBC cells. In vivo experiments, treatment of mice with cisplatin plus TRAIL resulted in a significant inhibition of CRL2335 xenograft tumors compared with untreated control tumors. Taken together the data suggest that cisplatin plus TRAIL treatment have the potential of providing a new strategy for improving the therapeutic outcome in TNBC patients.
Department of Pathology, Wayne State University, Detroit, Michigan 48201, USA.
Liping
L
Xu
Shuping
S
Yin
Sanjeev
S
Banerjee
Fazlul
F
Sarkar
Kaladhar B
KB
Reddy
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D051379:Mice; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency; D011960:Receptors, Estrogen / Q000172:deficiency; D011980:Receptors, Progesterone / Q000172:deficiency; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology / Q000627:therapeutic use*; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics
D002945:Cisplatin; D066246:ErbB Receptors; D051034:Inhibitor of Apoptosis Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012097:Repressor Proteins; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand; D015534:Trans-Activators; C117749:Birc5 protein, mouse; C486419:Trp63 protein, mouse; C524056:Erbb2 protein, mouse
Br J Cancer. 1992 Jun;65(6):787-93
1616849
Hum Pathol. 2006 Sep;37(9):1217-26
16938528
Cancer Res. 2010 Apr 1;70(7):2862-9
20215522
Anticancer Res. 2010 Feb;30(2):541-5
20332467
Cancer Chemother Pharmacol. 2008 May;61(6):965-71
17639392
Clin Cancer Res. 2004 Aug 15;10(16):5367-74
15328174
Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4429-34
17671126
Cancer. 2010 May 15;116(10):2401-8
20225327
Nat Rev Cancer. 2003 Jan;3(1):46-54
12509766
Cancer. 2007 Jan 1;109(1):25-32
17146782
Biochem Biophys Res Commun. 2006 Aug 11;346(4):1136-41
16793016
Histopathology. 2006 Jul;49(1):10-21
16842242
Breast Cancer Res. 2007;9(1):R16
17263897
Cancer Res. 1998 Dec 1;58(23):5315-20
9850056
Histopathology. 2008 Jan;52(1):108-18
18171422
Curr Opin Pharmacol. 2004 Aug;4(4):333-9
15251125
J Clin Oncol. 1988 Dec;6(12):1811-4
3199166
J Clin Invest. 2004 Oct;114(8):1117-27
15489959
Ann Oncol. 2008 Nov;19(11):1847-52
18567607
Blood. 2001 Nov 1;98(9):2603-14
11675328
Biochemistry. 2001 Jan 30;40(4):1117-23
11170436
Nat Med. 1999 Feb;5(2):157-63
9930862
J Clin Oncol. 2006 Dec 20;24(36):5652-7
17116942
Cancer Chemother Pharmacol. 1983;11(2):108-12
6685001
J Clin Invest. 2007 May;117(5):1370-80
17446929
Cancer Res. 2002 Jan 15;62(2):488-96
11809700
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74
11553815
J Biol Chem. 1999 Jun 18;274(25):17612-8
10364198
Breast Cancer Res. 2006;8(4):R34
16846532
Oncogene. 2005 Apr 28;24(19):3166-76
15735693
BMC Cancer. 2007 Jul 24;7:134
17650314
J Clin Oncol. 2005 Oct 10;23(29):7350-60
16145060
JAMA. 2006 Jun 7;295(21):2492-502
16757721
Br J Cancer. 2003 Apr 22;88(8):1285-91
12698198