Effects of 5-fluorouracil, adriamycin and irinotecan on HSC-39, a human scirrhous gastric cancer cell line

Tamaki,Rie; Kanai-Mori,Aya; Morishige,Yuta; Koike,Atsushi; Yanagihara,Kazuyoshi; Amano,Fumio

doi:10.3892/or.2017.5470

Effects of 5-fluorouracil, adriamycin and irinotecan on HSC-39, a human scirrhous gastric cancer cell line

Authors:
- Rie Tamaki
- Aya Kanai-Mori
- Yuta Morishige
- Atsushi Koike
- Kazuyoshi Yanagihara
- Fumio Amano
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Affiliations: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan
Published online on: February 20, 2017 https://doi.org/10.3892/or.2017.5470
Pages: 2366-2374

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Abstract

Therapies for patients with scirrhous gastric cancer remain ineffective. Current treatments for gastric cancer based on systemic therapy, such as the combination of S-1 with cisplatin or docetaxel, show good clinical response rates. S-1 plus cisplatin is the standard treatment for HER2-negative advanced scirrhous gastric cancer in Japan. In spite of recent advances in the treatment of gastric cancer, a standard chemotherapy regimen is yet to be established for scirrhous gastric cancer. To develop new therapeutic approaches based on characteristic biological features of cancer cells, we examined the mechanisms underlying the cytotoxicity of anticancer drugs and reactive oxygen species (ROS) toward a human scirrhous cancer cell line, HSC-39, in vitro. Anticancer drugs such as 5-fluorouracil (5-FU), adriamycin (ADR) and irinotecan (CPT-11), as well as ROS, were previously shown to have important cytotoxic effects on these tumor cells. We demonstrated that 5-FU effectively induced apoptosis in HSC-39 cells in a dose‑dependent manner, while ADR and CPT-11 induced necrosis and/or aponecrosis. 5-FU effectively inhibited WST-1 decrease in the MTT viability assay, even at low doses where little LDH release was observed, while ADR and CPT-11 only inhibited WST-1 decrease at high doses where LDH release was induced. Moreover, HSC-39 cells showed high sensitivity to H2O2 and NOC-18, but less sensitivity to other ROS, suggesting a link between cell damage and membrane permeability changes induced by H2O2 and NOC-18 or related oxygen radical species such as OH· or ·O2. These results suggest that combination treatment of chemotherapeutics with a fluoropyrimidine such as 5-FU is effective chemotherapy for scirrhous gastric cancer.

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1	Ikeguchi M, Miyake T, Matsunaga T, Yamamoto M, Fukumoto Y, Yamada Y, Fukuda K, Saito H, Tatebe S and Tsujitani S: Recent results of therapy for scirrhous gastric cancer. Surg Today. 39:290–294. 2009. View Article : Google Scholar : PubMed/NCBI
2	Hippo Y, Yashiro M, Ishii M, Taniguchi H, Tsutsumi S, Hirakawa K, Kodama T and Aburatani H: Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes. Cancer Res. 61:889–895. 2001.PubMed/NCBI
3	Kitamura K, Beppu R, Anai H, Ikejiri K, Yakabe S, Sugimachi K and Saku M: Clinicopathologic study of patients with Borrmann type IV gastric carcinoma. J Surg Oncol. 58:112–117. 1995. View Article : Google Scholar : PubMed/NCBI
4	Nakamura R, Saikawa Y, Wada N, Yoshida M, Kubota T, Kumai K and Kitajima M: Retrospective analysis of prognosis for scirrhous-type gastric cancer: One institution's experience. Int J Clin Oncol. 12:291–294. 2007. View Article : Google Scholar : PubMed/NCBI
5	Ohtsu A, Boku N, Yoshida S, Miyata Y, Shirao K, Shimada Y and Kurihara M: Japan Clinical Oncology Group: Response of the primary lesion in gastric cancer to chemotherapeutic trials. Int J Clin Onco1. 3:3–6. 1998. View Article : Google Scholar
6	Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, et al: S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): A phase III trial. Lancet Oncol. 9:215–221. 2008. View Article : Google Scholar : PubMed/NCBI
7	Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, et al: RAINBOW Study Group: Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol. 15:1224–1235. 2014. View Article : Google Scholar : PubMed/NCBI
8	Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, et al: REGARD Trial Investigators: Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): An international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 383:31–39. 2014. View Article : Google Scholar : PubMed/NCBI
9	Nashimoto A, Akazawa K, Isobe Y, Miyashiro I, Katai H, Kodera Y, Tsujitani S, Seto Y, Furukawa H, Oda I, et al: Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry. Gastric Cancer. 16:1–27. 2013. View Article : Google Scholar : PubMed/NCBI
10	Yanagihara K, Seyama T, Tsumuraya M, Kamada N and Yokoro K: Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the c-myc oncogene. Cancer Res. 51:381–386. 1991.PubMed/NCBI
11	Semba S, Kodama Y, Ohnuma K, Mizuuchi E, Masuda R, Yashiro M, Hirakawa K and Yokozaki H: Direct cancer-stromal interaction increases fibroblast proliferation and enhances invasive properties of scirrhous-type gastric carcinoma cells. Br J Cancer. 101:1365–1373. 2009. View Article : Google Scholar : PubMed/NCBI
12	Ishida M, Gomyo Y, Ohfuji S, Ikeda M, Kawasaki H and Ito H: Evidence that expression of a mutated p53 gene attenuates apoptotic cell death in human gastric intestinal-type carcinomas in vivo. Jpn J Cancer Res. 88:468–475. 1997. View Article : Google Scholar : PubMed/NCBI
13	Boku N, Yamamoto S, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Kimura A, et al: Randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG9912). J Clin Oncol 2007 ASCO Annual Meeting Proceedings. 25:LBA45132007.
14	Ichikawa W and Sasaki Y: Challenges in predicting the clinical outcome in S-1-based chemotherapy for gastric cancer patients. Int J Clin Oncol. 13:206–211. 2008. View Article : Google Scholar : PubMed/NCBI
15	Shitara K, Ishiguro A, Munakata M, Wada R and Sakata Y: Retrospective analysis of stage IV advanced gastric cancer treated with S-1 or other chemotherapy. Int J Clin Oncol. 11:367–374. 2006. View Article : Google Scholar : PubMed/NCBI
16	Sato K, Akaike T, Kojima Y, Ando M, Nagao M and Maeda H: Evidence of direct generation of oxygen free radicals from heterocyclic amines by NADPH/cytochrome P-450 reductase in vitro. Jpn J Cancer Res. 83:1204–1209. 1992. View Article : Google Scholar : PubMed/NCBI
17	Lanks KW, Gao JP and Sharma T: Photodynamic enhancement of doxorubicin cytotoxicity. Cancer Chemother Pharmacol. 35:17–20. 1994. View Article : Google Scholar : PubMed/NCBI
18	Kawakami T, Kawamura K, Fujimori K, Koike A and Amano F: Influence of the culture medium on the production of nitric oxide and expression of inducible nitric oxide synthase by activated macrophages in vitro. Biochem Biophys Rep. 5:328–334. 2016.
19	Leist M, Single B, Castoldi AF, Kühnle S and Nicotera P: Intracellular adenosine triphosphate (ATP) concentration: A switch in the decision between apoptosis and necrosis. J Exp Med. 185:1481–1486. 1997. View Article : Google Scholar : PubMed/NCBI
20	Simon HU, Haj-Yehia A and Levi-Schaffer F: Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis. 5:415–418. 2000. View Article : Google Scholar : PubMed/NCBI
21	Kinoshita T, Konishi M, Nakagohri T, Inoue K, Oda T, Takahashi S, Boku N, Ohtsu A and Yoshida S: Neoadjuvant chemotherapy with S-1 for scirrhous gastric cancer: A pilot study. Gastric Cancer. 6:(Suppl 1). S40–S44. 2003. View Article : Google Scholar
22	Ohtsu A: Current status and future prospects of chemotherapy for metastatic gastric cancer: A review. Gastric Cancer. 8:95–102. 2005. View Article : Google Scholar : PubMed/NCBI
23	Johnstone RW, Ruefli AA and Lowe SW: Apoptosis: A link between cancer genetics and chemotherapy. Cell. 108:153–164. 2002. View Article : Google Scholar : PubMed/NCBI
24	Johnston PG, Lenz HJ, Leichman CG, Danenberg KD, Allegra CJ, Danenberg PV and Leichman L: Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Res. 55:1407–1412. 1995.PubMed/NCBI
25	Yu R, Shtil AA, Tan TH, Roninson IB and Kong AN: Adriamycin activates c-jun N-terminal kinase in human leukemia cells: A relevance to apoptosis. Cancer Lett. 107:73–81. 1996. View Article : Google Scholar : PubMed/NCBI
26	Henkels KM and Turchi JJ: Cisplatin-induced apoptosis proceeds by caspase-3-dependent and -independent pathways in cisplatin-resistant and -sensitive human ovarian cancer cell lines. Cancer Res. 59:3077–3083. 1999.PubMed/NCBI
27	Marcelli M, Cunningham GR, Walkup M, He Z, Sturgis L, Kagan C, Mannucci R, Nicoletti I, Teng B and Denner L: Signaling pathway activated during apoptosis of the prostate cancer cell line LNCaP: Overexpression of caspase-7 as a new gene therapy strategy for prostate cancer. Cancer Res. 59:382–390. 1999.PubMed/NCBI
28	Matsura T, Kai M, Fujii Y, Ito H and Yamada K: Hydrogen peroxide-induced apoptosis in HL-60 cells requires caspase-3 activation. Free Radic Res. 30:73–83. 1999. View Article : Google Scholar : PubMed/NCBI
29	Ueta E, Yoneda K, Yamamoto T and Osaki T: Manganese superoxide dismutase negatively regulates the induction of apoptosis by 5-fluorouracil, peplomycin and gamma-rays in squamous cell carcinoma cells. Jpn J Cancer Res. 90:555–564. 1999. View Article : Google Scholar : PubMed/NCBI
30	Alexandre J, Nicco C, Chéreau C, Laurent A, Weill B, Goldwasser F and Batteux F: Improvement of the therapeutic index of anticancer drugs by the superoxide dismutase mimic mangafodipir. J Natl Cancer Inst. 98:236–244. 2006. View Article : Google Scholar : PubMed/NCBI
31	Yanagihara K and Tsumuraya M: Transforming growth factor β₁ induces apoptotic cell death in cultured human gastric carcinoma cells. Cancer Res. 52:4042–4045. 1992.PubMed/NCBI
32	Ohta S, Yanagihara K and Nagata K: Mechanism of apoptotic cell death of human gastric carcinoma cells mediated by transforming growth factor β. Biochem J. 324:777–782. 1997. View Article : Google Scholar : PubMed/NCBI
33	Romano G, Santi L, Bianco MR, Giuffrè MR, Pettinato M, Bugarin C, Garanzini C, Savarese L, Leoni S, Cerrito MG, et al: The TGF-β pathway is activated by 5-fluorouracil treatment in drug resistant colorectal carcinoma cells. Oncotarget. 7:22077–22091. 2016.PubMed/NCBI
34	Liu RM and Desai LP: Reciprocal regulation of TGF-β and reactive oxygen species: A perverse cycle for fibrosis. Redox Biol. 6:565–577. 2015. View Article : Google Scholar : PubMed/NCBI
35	Pan X, Zhang X, Sun H, Zhang J, Yan M and Zhang H: Autophagy inhibition promotes 5-fluorouraci-induced apoptosis by stimulating ROS formation in human non-small cell lung cancer A549 cells. PLoS One. 8:e566792013. View Article : Google Scholar : PubMed/NCBI
36	Rosenberg B: Fundamental studies with cisplatin. Cancer. 55:2303–l6. 1985. View Article : Google Scholar : PubMed/NCBI
37	Hecquet B, Vennin P, Fournier C, Lefebvre JL, Caty A, Bonneterre J, Adenis L and Demaille A: Platinum concentration in human tumors of head and neck, uterine cervix, and breast following treatment with cisplatin. Cancer Chemother Pharmacol. 15:310–312. 1985. View Article : Google Scholar : PubMed/NCBI
38	Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, et al: Japan Clinical Oncology Group Study (JCOG9205): Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol. 21:54–59. 2003. View Article : Google Scholar : PubMed/NCBI