The subunits of glutamate cysteine ligase enhance cisplatin resistance in human non-small cell lung cancer xenografts in vivo

  • Authors:
    • Sakashi Fujimori
    • Yoshiyuki Abe
    • Masatake Nishi
    • Atsushi Hamamoto
    • Yoshimasa Inoue
    • Yasuyuki Ohnishi
    • Chiyoko Nishime
    • Hozumi Matsumoto
    • Hitoshi Yamazaki
    • Hiroshi Kijima
    • Yoshito Ueyama
    • Hiroshi Inoue
    • Masato Nakamura
  • View Affiliations

  • Published online on: August 1, 2004     https://doi.org/10.3892/ijo.25.2.413
  • Pages: 413-418
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Abstract

Glutamate cysteine ligase (GCL) is a key enzyme in glutathione (GSH) synthesis, and is thought to play a significant role in the intracellular detoxification of anticancer drugs, especially of cisplatin (CDDP). GCL is composed of a modifier or light chain subunit (GCLM) and a catalytic or heavy chain subunit (GCLC). It was unclear whether the subunits are essential to CDDP-resistance. We examined the gene expression of GCLM and GCLC in 39 xenografts of human non-small cell lung cancer [NSCLC; 10 adenocarcinoma (Ad), 17 squamous cell carcinoma (Sq) and 12 large cell carcinoma (La)] by real-time polymerase chain reaction (PCR) with human-specific primers. Drug sensitivity to CDDP was evaluated in the 9 xenografts (4 Ad, 2 Sq and 3 La) using an in vivo drug sensitivity test. There was a significant association between the expression of GCLM and GCLC mRNA in each xenograft (Fisher's test, p<0.045). Squamous cell carcinoma xenografts significantly showed higher expression of GCLM gene than adenocarcinoma xenografts (p=0.023, t-test), while there was no significant difference in GCLC gene expression levels between each histopathological xenograft. Three of nine xenografts were sensitive to CDDP (Mann-Whitney U test, p<0.01, one-sided), while the other 6 xenografts were resistant. There was a significant relationship between drug sensitivity to CDDP and the co-overexpression of GCL subunits (χ2 test for independence, Yates' correction, p=0.014). These results suggested that the co-overexpression of GCL subunits correlated with CDDP-resistance in human NSCLC xenograft in vivo.

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August 2004
Volume 25 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Fujimori S, Abe Y, Nishi M, Hamamoto A, Inoue Y, Ohnishi Y, Nishime C, Matsumoto H, Yamazaki H, Kijima H, Kijima H, et al: The subunits of glutamate cysteine ligase enhance cisplatin resistance in human non-small cell lung cancer xenografts in vivo. Int J Oncol 25: 413-418, 2004
APA
Fujimori, S., Abe, Y., Nishi, M., Hamamoto, A., Inoue, Y., Ohnishi, Y. ... Nakamura, M. (2004). The subunits of glutamate cysteine ligase enhance cisplatin resistance in human non-small cell lung cancer xenografts in vivo. International Journal of Oncology, 25, 413-418. https://doi.org/10.3892/ijo.25.2.413
MLA
Fujimori, S., Abe, Y., Nishi, M., Hamamoto, A., Inoue, Y., Ohnishi, Y., Nishime, C., Matsumoto, H., Yamazaki, H., Kijima, H., Ueyama, Y., Inoue, H., Nakamura, M."The subunits of glutamate cysteine ligase enhance cisplatin resistance in human non-small cell lung cancer xenografts in vivo". International Journal of Oncology 25.2 (2004): 413-418.
Chicago
Fujimori, S., Abe, Y., Nishi, M., Hamamoto, A., Inoue, Y., Ohnishi, Y., Nishime, C., Matsumoto, H., Yamazaki, H., Kijima, H., Ueyama, Y., Inoue, H., Nakamura, M."The subunits of glutamate cysteine ligase enhance cisplatin resistance in human non-small cell lung cancer xenografts in vivo". International Journal of Oncology 25, no. 2 (2004): 413-418. https://doi.org/10.3892/ijo.25.2.413