Concentration-dependent collateral sensitivity of cisplatin-resistant gastric cancer cell sublines

https://doi.org/10.1016/j.bbrc.2005.01.015Get rights and content

Abstract

The cisplatin-resistant gastric cancer cell sublines, SNU-601/Cis2 and /Cis10, were 49 and >530 times more resistant to cisplatin, respectively, compared with the drug-sensitive cells, SNU-601/WT. The SNU-601/Cis2 showed cross-resistance to carboplatin, heptaplatin, doxorubicin, mitomycin C, and 5-fluorouracil compared with the SNU-601/WT whereas the SNU-601/Cis10 displayed collateral sensitivity to these drugs with the exception of cisplatin compared with the SNU-601/Cis2, suggesting that the cross-resistance and collateral sensitivity of cisplatin-resistant gastric cancer cells are dependent upon cisplatin concentrations. Altered expression of the antioxidant and transporter genes (metallothionein, catalase, superoxide dismutases, P-glycoprotein, and the breast cancer resistance protein) was involved in these phenotypes of the cisplatin-resistant gastric cancer cell lines.

Section snippets

Materials and methods

Cell culture and the selection of the gastric cancer cell sublines for cisplatin resistance. The human gastric cancer cell line, SNU-601, was obtained from the Cancer Research Center in Seoul National University (South Korea). The cells were cultured in RPMI 1640 (Gibco-BRL, Grand Island, NY, USA) supplemented with 10% FBS (Sigma Chemical, St. Louis, MO, USA). The cells were maintained as a monolayer culture and were subcultured at confluence. The cisplatin-resistant gastric cancer cell subline

Sensitivity of cisplatin-resistant gastric cancer cell sublines to various anticancer drugs

Of the eight human gastric cancer cell lines (SNU-1, SNU-5, SNU-16, SNU-484, SNU-601, SNU-620, SNU-638, and SNU-668), the SNU-601 cells were chosen owing to their having the lowest MT mRNA expression level. The cisplatin-resistant gastric cancer cell lines, SNU-601/Cis2 and /Cis10, which were selected by the chronic exposure to 2 and 10 μg/ml cisplatin, respectively, were 49 and >530 times more resistant to cisplatin than the parental SNU-601 cells (SNU-601/WT), respectively (Fig. 1). As shown

Discussion

The cisplatin analogs are among the most active and widely used cytotoxic anticancer drugs. However, the acquisition or presence of resistance significantly undermines the curative potential of these drugs against many malignancies [5]. In this study, two cisplatin-resistant gastric cancer cell sublines, SNU-601/Cis2 and /Cis10, were found to be resistant to cisplatin and various anticancer drugs including carboplatin, heptaplatin, mitomycin C, doxorubicin, and 5-fluorouracil. Interestingly,

Acknowledgments

This work was supported, in part, by grants from the Ministry of Science and Technology, Korea, and the Korea Science and Engineering Foundation through the Research Center for Resistant Cells (R13-2003-009).

References (24)

  • H. Bier

    Circumvention of drug resistance in cisplatin-resistant sublines of the human squamous carcinoma cell line HLac 79 in vitro and in vivo

    Acta Otolaryngol.

    (1991)
  • P.A. Andrews et al.

    Metallothionein-mediated cisplatin resistance in human ovarian carcinoma cells

    Cancer Chemother. Pharmacol.

    (1987)
  • Cited by (32)

    • Caveolin-1 promotes radioresistance in rhabdomyosarcoma through increased oxidative stress protection and DNA repair

      2021, Cancer Letters
      Citation Excerpt :

      Catalase is a homo-tetrameric enzyme (EC 1.11.1.6) responsible for the decomposition of H2O2 [47,53], whose overexpression has been shown to protect cells against DNA damage induced by UVB and X-rays [54,55]. It is considered a hallmark of aggressive cancers that develop resistance to chronic exposure to various agents [56], such as cisplatin [57], bleomycin [58], and radiotherapy [59]. A link between Cav-1 and H2O2 production has emerged in recent years since Cav-1 has been reported to attenuate the production of H2O2 [60] and limit DNA damage in lung cancer cells [61], while its loss promotes oxidative stress in the tumor microenvironment via increased H2O2 production [62].

    • Regulation of catalase expression in healthy and cancerous cells

      2015, Free Radical Biology and Medicine
      Citation Excerpt :

      Increased catalase expression has been observed in tumors from patients with gastric carcinoma, skin cancer, and chronic myeloid leukemia [50–53] and in human HL-60 cancer cells rendered resistant to chronic exposure to H2O2 [54–56]. This high catalase expression has also been observed in several human cancer cell lines (e.g., gastric, oral, pancreatic, bladder) exposed to cisplatin [57], ascorbic acid [58], bleomycin [59], gemcitabine [60], mitomycin C [61], hormonal therapy [62], and ionizing radiation [63]. The importance of catalase for human life is illustrated by the diseases that are associated with mutations of its gene.

    • Catalase overexpression in mammary cancer cells leads to a less aggressive phenotype and an altered response to chemotherapy

      2011, Biochemical Pharmacology
      Citation Excerpt :

      Catalase is also down-regulated in healthy cells transformed with T-antigen of SV40 or Ras, although the underlying mechanisms of this down-regulation are still unknown [34,35]. Interestingly, it has also been observed that catalase levels are modified (increase or decrease) in cancer cell lines resistant to some chemotherapeutic agents or hydrogen peroxide [36–42]. Given the increasing development of pro-oxidant approaches for treating cancer, we investigated whether the modulation of the antioxidant capacities affects the survival of cancer cells exposed to such agents.

    View all citing articles on Scopus
    View full text