[Effect of phenylhexyl isothiocyanate on adriamycin resistance of K562/A02 cell line].
This study was to investigate the effect of phenylhexyl isothiocyanate (PHI) on drug resistance and sensitivity on K562/A02 cell line to adriamycin (ADM) and to elucidate the possible mechanisms. The inhibition rates of ADM and PHI + ADM on growth of K562/A02 cell line were measured by MTT assay, and K562/A02 cell resistant multiple was calculated. The apoptosis rate of K562/A02 cell line, the changes of intracellular ADM concentrations and MRP1 protein level were detected by flow cytometry (FCM). Intracellular reoxidized GSH level was determined by spectrometric enzyme assay and MRP1 mRNA was assayed by semiquantitative RT-PCR before and after using PHI. The results indicated that the survival rate of K562/A02 cell line decreased with the increasing concentration of PHI. Apoptosis rate increased after treatment in combination with two above drugs, the changes of drug resistance multiple and intracellular ADM level had statistical significance between K562/A02 and K562 cells (p < 0.05), when the concentration of PHI was more than 20 micromol/L. Intracellular GSH level in K562/A02 cell line reduced 5% when 1 microg/ml ADM was used alone, and it increased slightly at first, then decreased when more than 10 micromol/L PHI was used. When more than 20 micromol/L PHI was used in combination with 1 microg/ml ADM, intracellular GSH level in K562/A02 cell line decreased progressively with increasing the concentration of PHI. The expressions of MRP1 mRNA and protein had no statistical significance between K562/A02 and K562 cells (p > 0.05) after or before PHI was used. It is concluded that the cyto-toxicity of PHI to K562/A02 cell line does not associate with the depletion of the intracellular GSH. PHI not only enhances the sensitivity of K562/A02 cell line to ADM, but also partially reverses effect of K562/A02 cell resistance to ADM. ADM combined with PHI can diminish side effect and dosage of ADM.
Yuang
Peng
P
Department of Hematology, Zhongda Hospital, College of Clinical Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China.
Chen
Bao-An
BA
Cheng
Jian
J
Ma
Xu-Dong
XD
Liu
De-Long
DL
Lu
Quan-Yi
QY
D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D020014:K562 Cells
D017879:Isothiocyanates; C073279:6-phenylhexyl isothiocyanate; D004317:Doxorubicin