Factors involved in the cisplatin resistance of KCP‑4 human epidermoid carcinoma cells

Oiso,Shigeru; Takayama,Yui; Nakazaki,Rie; Matsunaga,Naoko; Motooka,Chie; Yamamura,Asuka; Ikeda,Ryuji; Nakamura,Kazuo; Takeda,Yasuo; Kariyazono,Hiroko

doi:10.3892/or.2013.2896

Factors involved in the cisplatin resistance of KCP‑4 human epidermoid carcinoma cells

Authors:
- Shigeru Oiso
- Yui Takayama
- Rie Nakazaki
- Naoko Matsunaga
- Chie Motooka
- Asuka Yamamura
- Ryuji Ikeda
- Kazuo Nakamura
- Yasuo Takeda
- Hiroko Kariyazono
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Affiliations: Department of Pharmaceutical Health Care Sciences, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan, Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890‑8520, Japan, Department of Biopharmaceutics, Nihon Pharmaceutical University, Saitama 362-0806, Japan
Published online on: December 5, 2013 https://doi.org/10.3892/or.2013.2896
Pages: 719-726

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Abstract

KCP-4 is a cisplatin-resistant cell line established from human epidermoid carcinoma KB-3-1 cells. Although our previous study revealed that one of the mechanisms for cisplatin resistance in KCP-4 cells is the activation of NF-κB, its high resistance is considered to be induced by multiple mechanisms. In the present study, we explored other factors involved in the development of cisplatin resistance in KCP-4 cells. Since it has been reported that an unknown efflux pump exports cisplatin from KCP-4 cells in an ATP-dependent manner, we examined 48 types of ATP-binding cassette proteins as candidate cisplatin efflux transporters. The mRNA expression levels of ABCA1, ABCA3, ABCA7 and ABCB10 in KCP-4 cells were higher when compared to those in KB-3-1 cells. These expression levels in cisplatin-sensitive revertant KCP-4 cells (KCP-4R cells), were reduced in parallel with the sensitivity of these cells to cisplatin and their intracellular accumulation of cisplatin. Next, we investigated the occurrence of mutations in p53 in KCP-4 cells. We found a heterozygous missense mutation at codon 72 (p.Pro72Arg) in p53 of both KCP-4 and KB-3-1 cells, but the protein expression level of p53 in KCP-4 cells was higher when compared to that in KB-3-1. These results suggest that ABCA1, ABCA3, ABCA7 and ABCB10 are candidate genes for the cisplatin efflux transporter that is involved in the cisplatin resistance of KCP-4 cells, and that the mutation at codon 72 of p53 may contribute to the development of cisplatin resistance.

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1	Loehrer PJ and Einhorn LH: Drugs five years later. Cisplatin Ann Intern Med. 100:704–713. 1984.PubMed/NCBI
2	Elit L, Oliver TK, Covens A, et al: Intraperitoneal chemotherapy in the first-line treatment of women with stage III epithelial ovarian cancer: a systematic review with metaanalyses. Cancer. 109:692–702. 2007. View Article : Google Scholar : PubMed/NCBI
3	Sculier JP and Moro-Sibilot D: First- and second-line therapy for advanced nonsmall cell lung cancer. Eur Respir J. 33:915–930. 2009. View Article : Google Scholar : PubMed/NCBI
4	Vermorken JB and Specenier P: Optimal treatment for recurrent/metastatic head and neck cancer. Ann Oncol. 21(Suppl 7): vii252–261. 2010. View Article : Google Scholar : PubMed/NCBI
5	Ismaili N, Amzerin M and Flechon A: Chemotherapy in advanced bladder cancer: current status and future. J Hematol Oncol. 4:352011. View Article : Google Scholar : PubMed/NCBI
6	Comess KM, Burstyn JN, Essigmann JM and Lippard SJ: Replication inhibition and translesion synthesis on templates containing site-specifically placed cis-diamminedichloroplatinum(II) DNA adducts. Biochemistry. 31:3975–3990. 1992. View Article : Google Scholar : PubMed/NCBI
7	Suo Z, Lippard SJ and Johnson KA: Single d(GpG)/cis-diammineplatinum(II) adduct-induced inhibition of DNA polymerization. Biochemistry. 38:715–726. 1999. View Article : Google Scholar : PubMed/NCBI
8	Wang G, Reed E and Li QQ: Molecular basis of cellular response to cisplatin chemotherapy in non-small cell lung cancer (Review). Oncol Rep. 12:955–965. 2004.PubMed/NCBI
9	Siddik ZH: Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 22:7265–7279. 2003. View Article : Google Scholar : PubMed/NCBI
10	Kelland LR: New platinum antitumor complexes. Crit Rev Oncol Hematol. 15:191–219. 1993. View Article : Google Scholar : PubMed/NCBI
11	Timmer-Bosscha H, Mulder NH and de Vries EG: Modulation of cis-diamminedichloroplatinum(II) resistance: a review. Br J Cancer. 66:227–238. 1992. View Article : Google Scholar : PubMed/NCBI
12	Borst P, Rottenberg S and Jonkers J: How do real tumors become resistant to cisplatin? Cell Cycle. 7:1353–1359. 2008. View Article : Google Scholar : PubMed/NCBI
13	Torigoe T, Izumi H, Ishiguchi H, et al: Cisplatin resistance and transcription factors. Curr Med Chem Anticancer Agents. 5:15–27. 2005. View Article : Google Scholar : PubMed/NCBI
14	Stewart DJ: Mechanisms of resistance to cisplatin and carboplatin. Crit Rev Oncol Hematol. 63:12–31. 2007. View Article : Google Scholar : PubMed/NCBI
15	Safaei R and Howell SB: Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs. Crit Rev Oncol Hematol. 53:13–23. 2005. View Article : Google Scholar : PubMed/NCBI
16	Ishida S, Lee J, Thiele DJ and Herskowitz I: Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals. Proc Natl Acad Sci USA. 99:14298–14302. 2002. View Article : Google Scholar : PubMed/NCBI
17	Miyashita H, Nitta Y, Mori S, et al: Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin. Oral Oncol. 39:157–162. 2003. View Article : Google Scholar : PubMed/NCBI
18	Samimi G, Safaei R, Katano K, et al: Increased expression of the copper efflux transporter ATP7A mediates resistance to cisplatin, carboplatin, and oxaliplatin in ovarian cancer cells. Clin Cancer Res. 10:4661–4669. 2004. View Article : Google Scholar : PubMed/NCBI
19	Surowiak P, Materna V, Kaplenko I, et al: ABCC2 (MRP2, cMOAT) can be localized in the nuclear membrane of ovarian carcinomas and correlates with resistance to cisplatin and clinical outcome. Clin Cancer Res. 12:7149–7158. 2006. View Article : Google Scholar : PubMed/NCBI
20	Taniguchi K, Wada M, Kohno K, et al: A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Res. 56:4124–4129. 1996.
21	Fujii R, Mutoh M, Sumizawa T, Chen ZS, Yoshimura A and Akiyama S: Adenosine triphosphate-dependent transport of leukotriene C₄ by membrane vesicles prepared from cisplatin-resistant human epidermoid carcinoma tumor cells. J Natl Cancer Inst. 86:1781–1784. 1994.PubMed/NCBI
22	Fujii R, Mutoh M, Niwa K, Yamada K, Aikou T, Nakagawa M, Kuwano M and Akiyama S: Active efflux system for cisplatin in cisplatin-resistant human KB cells. Jpn J Cancer Res. 85:426–433. 1994. View Article : Google Scholar : PubMed/NCBI
23	Oiso S, Ikeda R, Nakamura K, Takeda Y, Akiyama S and Kariyazono H: Involvement of NF-κB activation in the cisplatin resistance of human epidermoid carcinoma KCP-4 cells. Oncol Rep. 28:27–32. 2012.
24	Chen ZS, Mutoh M, Sumizawa T, et al: An active efflux system for heavy metals in cisplatin-resistant human KB carcinoma cells. Exp Cell Res. 240:312–320. 1998. View Article : Google Scholar : PubMed/NCBI
25	Chuman Y, Chen ZS, Sumizawa T, et al: Characterization of the ATP-dependent LTC₄ transporter in cisplatin-resistant human KB cells. Biochem Biophys Res Commun. 226:158–165. 1996. View Article : Google Scholar : PubMed/NCBI
26	Velculescu VE and El-Deiry WS: Biological and clinical importance of the p53 tumor-suppressor gene. Clin Chem. 42:858–868. 1996.PubMed/NCBI
27	El-Deiry WS: The role of p53 in chemosensitivity and radiosensitivity. Oncogene. 22:7486–7495. 2003. View Article : Google Scholar : PubMed/NCBI
28	Hussain SP and Harris CC: Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes. Cancer Res. 58:4023–4037. 1998.
29	Akiyama S, Fojo A, Hanover JA, Pastan I and Gottesman MM: Isolation and genetic characterization of human KB cell lines resistant to multiple drugs. Somat Cell Mol Genet. 11:117–126. 1985. View Article : Google Scholar : PubMed/NCBI
30	Tanaka AR, Abe-Dohmae S, Ohnishi T, et al: Effects of mutations of ABCA1 in the first extracellular domain on subcellular trafficking and ATP binding/hydrolysis. J Biol Chem. 278:8815–8819. 2003. View Article : Google Scholar : PubMed/NCBI
31	Nagao K, Takahashi K, Hanada K, Kioka N, Matsuo M and Ueda K: Enhanced apoA–I-dependent cholesterol efflux by ABCA1 from sphingomyelin-deficient Chinese hamster ovary cells. J Biol Chem. 282:14868–14874. 2007.
32	Iwasaki H, Okabe T, Takara K, Yoshida Y, Hanashiro K and Oku H: Down-regulation of lipids transporter ABCA1 increases the cytotoxicity of nitidine. Cancer Chemother Pharmacol. 66:953–959. 2010. View Article : Google Scholar : PubMed/NCBI
33	Bachmeier BE, Iancu CM, Killian PH, et al: Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells. Mol Cancer. 8:1292009. View Article : Google Scholar : PubMed/NCBI
34	Lee BH, Taylor MG, Robinet P, et al: Dysregulation of cholesterol homeostasis in human prostate cancer through loss of ABCA1. Cancer Res. 73:1211–1218. 2013. View Article : Google Scholar : PubMed/NCBI
35	Sekine Y, Demosky SJ, Stonik JA, et al: High-density lipoprotein induces proliferation and migration of human prostate androgen-independent cancer cells by an ABCA1-dependent mechanism. Mol Cancer Res. 8:1284–1294. 2010. View Article : Google Scholar
36	Matsumura Y, Sakai H, Sasaki M, Ban N and Inagaki N: ABCA3-mediated choline-phospholipids uptake into intracellular vesicles in A549 cells. FEBS Lett. 581:3139–3144. 2007. View Article : Google Scholar : PubMed/NCBI
37	Matsumura Y, Ban N, Ueda K and Inagaki N: Characterization and classification of ATP-binding cassette transporter ABCA3 mutants in fatal surfactant deficiency. J Biol Chem. 281:34503–34514. 2006. View Article : Google Scholar : PubMed/NCBI
38	Chapuy B, Koch R, Radunski U, et al: Intracellular ABC transporter A3 confers multidrug resistance in leukemia cells by lysosomal drug sequestration. Leukemia. 22:1576–1586. 2008. View Article : Google Scholar : PubMed/NCBI
39	Chapuy B, Panse M, Radunski U, et al: ABC transporter A3 facilitates lysosomal sequestration of imatinib and modulates susceptibility of chronic myeloid leukemia cell lines to this drug. Haematologica. 94:1528–1536. 2009. View Article : Google Scholar : PubMed/NCBI
40	Iwamoto N, Abe-Dohmae S, Sato R and Yokoyama S: ABCA7 expression is regulated by cellular cholesterol through the SREBP2 pathway and associated with phagocytosis. J Lipid Res. 47:1915–1927. 2006. View Article : Google Scholar : PubMed/NCBI
41	Karch CM, Jeng AT, Nowotny P, Cady J, Cruchaga C and Goate AM: Expression of novel Alzheimer's disease risk genes in control and Alzheimer's disease brains. PLoS One. 7:e509762012.
42	Kim WS, Li H, Ruberu K, et al: Deletion of Abca7 increases cerebral amyloid-β accumulation in the J20 mouse model of Alzheimer's disease. J Neurosci. 33:4387–4394. 2013.PubMed/NCBI
43	Graf SA, Haigh SE, Corson ED and Shirihai OS: Targeting, import, and dimerization of a mammalian mitochondrial ATP binding cassette (ABC) transporter, ABCB10 (ABC-me). J Biol Chem. 279:42954–42963. 2004. View Article : Google Scholar : PubMed/NCBI
44	Shirihai OS, Gregory T, Yu C, Orkin SH and Weiss MJ: ABC-me: a novel mitochondrial transporter induced by GATA-1 during erythroid differentiation. EMBO J. 19:2492–2502. 2000. View Article : Google Scholar : PubMed/NCBI
45	Chen W, Dailey HA and Paw BH: Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesis. Blood. 116:628–630. 2010. View Article : Google Scholar : PubMed/NCBI
46	Chen W, Paradkar PN, Li L, et al: Abcb10 physically interacts with mitoferrin-1 (Slc25a37) to enhance its stability and function in the erythroid mitochondria. Proc Natl Acad Sci USA. 106:16263–16268. 2009. View Article : Google Scholar : PubMed/NCBI
47	Ishikawa T, Li ZS, Lu YP and Rea PA: The GS-X pump in plant, yeast, and animal cells: structure, function, and gene expression. Biosci Rep. 17:189–207. 1997. View Article : Google Scholar : PubMed/NCBI
48	Bergamaschi D, Gasco M, Hiller L, et al: p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. Cancer Cell. 3:387–402. 2003. View Article : Google Scholar : PubMed/NCBI