Effects of functional inhibition of p-glycoprotein on radiosensitivity of drug-resistant MCF-7/Adr tumor cells

Abstract

Abstract: Objective To observe the effects of functional inhibition of p-glycoprotein on radiosensitivity of drug-resistant MCF-7/Adr tumor cells. Methods Flow cytometry was used to examine the dynamic changes of apoptosis rate and mito- chondrial membrane potential (ΔΨm) in verapamil-treated and untreated MCF-7/Adr cells after the X-ray exposure. Results The apoptotic rate of verapamil-treated cells was 25.53%±2.85%, 30.43%±2.21%, 39.03%±2.60% at 6, 12, and 24 h after X-ray exposure, respectively, and was 16.13%±1.16%, 21.73%±1.31% and 27.53%±2.55% for the untreated cells. The mean fluorescence intensity of verapamil-treated cells was 75.27±4.90, 96.47±5.59, 57.77±2.55 responding time points, in comparison with the intensity of 54.17±4.05, 62.30±5.93, and 39.53±2.65, for the untreated cells were significantly higher than those in the untreated cells at each of the specified time point (P<0.01), and in the former cells, the apoptosis rate reached the maximum at 24 h (F=47.870, P=0.000) and the ΔΨm at 12 h after X-ray exposure (F=74.485, P=0.000). Conclusion The radiosensitivity of MCF-7/Adr cells is increased after functional inhibition of p-glycoprotein, possibly in relation to the alteration of ΔΨm.

CLC Number:

R329.25
R733

YU Zhi-jian¹, CHEN Jun², YUAN Ya-wei², XIAO Ming-xing², CHEN Chun². Effects of functional inhibition of p-glycoprotein on radiosensitivity of drug-resistant MCF-7/Adr tumor cells[J]. Journal of Southern Medical University, 2004, 24(08): 885-887.

References

[1] Johnstone RW, Ruefli AA, Tainton KM, et al. A role for p-glycoprotein in regulating cell death[J]. Leuk Lymphoma, 2000, 38(1-2):1-11.
[2] Ruefli AA, Bernhard D, Tainton KM, et al. Suberoylanilide hydroxamic acid (SAHA) overcomes multidrug resistance and induces cell death in p-glycoprotein-expressing cells[J]. Int J Cancer, 2002,99(2): 292-8.
[3] 袁亚维,张积仁,周殿元,等.Ribozyme基因对人肿瘤细胞株MCF-7/Adr多药抗药性的靶向逆转[J].中华医学杂志,1997,77(7):494-6.Yuan YW, Zhang JR, Zhou DY, et al. The reversion of multidrug resistance in tumor cell line MCF-7/Adr by ribozyme[J]. Natl Med J Chin, 1997, 77(7): 494-6.
[4] Lyng FM, Seymour CB, Mothersill C. Initiation ofapoptosis in cells exposed to medium from the progeny of irradiated cells: a possible mechanism for bystander-induced genomic instability[J]. Radiat Res, 2002, 157(4): 365-70.
[5] Liu ZL, Onda K, Tanaka S, et al. Induction ofmultidrug resistance in MOLT-4 cells by anticancer agents is closely related to increased expression of functional p-glycoprotein and MDR1 mRNA[J].Cancer Chemother Pharmacol, 2002, 49(5): 391-7.
[6] Ushmorov A, Ratter F, Lehmann V, et al. Nitric oxide-induced apoptosis in human leukemic lines requires mitochondrial lipid degradation and cytochrome c release[J]. Blood, 1999, 93(7): 2342-52.
[7] Gollapud S, Gupda S. Anti-p-plycoprotein antibody-induced apoptosis of activated peripheral blood lymphocytes: a possible role of p-plycoprotein in lymphocyte survival[J]. J Clin Immunol, 2001,21 (6): 420-30.
[8] NotarbartoloM, Cervello M, Dusonchet L, et al. Resistance to diverse apoptotic triggers in multidrug resistant HL60 cells and its possible relationship to the expression ofp-plycoprotein, Fas and of the novel anti-apoptosis factors IAP (inhibitory of apoptosis proteins)[J]. Cancer Lett, 2002, 180(1): 91-101.
[9] Canton M, Caffieri D, Dali F, et al. PUVA-induced apoptosis involves mitoehondrial dysfunction caused by the opening of the permeability transition pore[J]. FEBS Lett, 2002, 522(1-3): 168-72.
[10] Ruth AC, Roninson IB. Effects of the multidrug transporter p-plycoprotein on cellular responses to ionizing radiation[J]. Cancer Res,2000, 60: 2576-78.
[11] Ogawa Y, Nishioka A, Kobayashi T, et al. Radiation-induced apoptosis of human peripheral T cells: analyses with cDNA expression arrays and mitochondrial membrance potential assay[J]. Int Mol Med, 2001, 7(6): 603-7.