Response of brain specific microenvironment to P-glycoprotein inhibitor: An important factor determining therapeutic effect of P-glycoprotein inhibitor on brain metastatic tumors

  • Authors: Kyeung Min Joo, Sang Yong Song, Kwan Park, Mi Hyun Kim, Juyoun Jin, Bong Gu Kang, Mi Jung Jang, Gwan Sun Lee, Maeng Sup Kim, Do-Hyun Nam
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  • Published online on: Wednesday, October 1, 2008
  • Pages: 705-712
  • DOI: 10.3892/ijo_00000056

Abstract

P-glycoprotein (P-gp), a factor responsible for the multidrug resistance of tumors, is specifically expressed in brain microenvironment. To test its roles in brain metastatic tumor chemoresistance, we implanted the paclitaxel-sensitive melanoma cell line, K1735, into the skin or brain of mice and examined its paclitaxel resistances. When implanted into the skin, paclitaxel inhibited tumor growth, however, it had no inhibitory effect on cells implanted into the brain. The paclitaxel resistance of the brain K1735 tumors was eliminated by combined treatment with a P-gp inhibitor, HM30181A, and paclitaxel. Previously we found that there is a defined therapeutic window for combined treatment of brain tumors with HM30181A and paclitaxel. To determine whether it is due to responses of the brain microenvironment we measured changes in P-gp expression and function of brain endothelial cells in response to HM30181A treatment in vitro and in vivo. They were significantly increased by high-dose HM30181A treatment and it was related with the therapeutic effect loss of high-dose HM30181A treatment. Therefore, P-gp in the brain microenvironment has crucial roles in the brain metastatic tumor chemoresistance and brain microenvironment responses to P-gp inhibitor treatment should be considered in the development of brain endothelial cell-targeted chemotherapy using P-gp inhibitor.
Journal Cover

October 2008
Volume 33 Issue 4

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

2012 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Joo, K., Song, S., Park, K., Kim, M., Jin, J., Kang, B., Jang, M., Lee, G., Kim, M., & Nam, D. (2008). Response of brain specific microenvironment to P-glycoprotein inhibitor: An important factor determining therapeutic effect of P-glycoprotein inhibitor on brain metastatic tumors. International Journal of Oncology, 33(4), 705-712.
MLA
Joo, Song, Park, Kim, Jin, Kang, Jang, Lee, Kim, and Do-Hyun Nam. "Response of brain specific microenvironment to P-glycoprotein inhibitor: An important factor determining therapeutic effect of P-glycoprotein inhibitor on brain metastatic tumors." International Journal of Oncology International Journal of Oncology 33.4 (2008): 705-712.
Chicago
Joo, Song, Park, Kim, Jin, Kang, Jang, Lee, Kim, and Do-Hyun Nam. "Response of brain specific microenvironment to P-glycoprotein inhibitor: An important factor determining therapeutic effect of P-glycoprotein inhibitor on brain metastatic tumors." International Journal of Oncology International Journal of Oncology 33 no. 4 (2008): 705-712.