Selectively induced high MRP gene expression in multidrug-resistant human HL60 leukemia cells

Wada, Hideo; Saikawa, Yoshiro; Niida, Yo; Nishimura, Ryosei; Noguchi, Tadashi; Matsukawa, Harumi; Ichihara, Tomofumi; Koizumi, Satoshi

doi:10.1016/s0301-472x(98)00027-7

Cited by 21 publications

(14 citation statements)

References 31 publications

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“…Wada et al [18] showed that the multi-drug resistance of HL-60/DOX was attributable to the high levels of MRP expression in the HL60/DOX cells, and high expressing MRP induced the alteration of the drug accumulation from enhanced efflux. We used RT-PCR and western blot analysis to detect the MRP expression and found that MRP expression was remarkably increased in HL-60/A cells.…”

Section: Discussionmentioning

confidence: 99%

SKP2 siRNA inhibits the degradation of P27<sup>kip1</sup> and down-regulates the expression of MRP in HL-60/A cells

Xiao¹,

Su²,

Li³

et al. 2009

ABBS

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S-phase kinase-associated protein 2 (SKP2) gene is a tumor suppressor gene, and is involved in the ubiquitinmediated degradation of P27 kip1 . SKP2 and P27 kip1 affect the proceeding and prognosis of leukemia through regulating the proliferation, apoptosis and differentiation of leukemia cells. In this study, we explored the mechanism of reversing of HL-60/A drug resistance through SKP2 down-regulation. HL-60/A cells were nucleofected by Amaxa Nucleofector System with SKP2 siRNA. The gene and protein expression levels of Skp2, P27 kip1 , and multi-drug resistance associated protein (MRP) were determined by reverse transcription-polymerase chain reaction and western blot analysis, respectively. The cell cycle was analyzed by flow cytometry. The 50% inhibitory concentration value was calculated using cytotoxic analysis according to the death rate of these two kinds of cells under different concentrations of chemotherapeutics to compare the sensitivity of the cells. HL-60/A cells showed multi-drug resistance phenotype characteristic by cross-resistance to adriamycin, daunorubicin, and arabinosylcytosine, due to the expression of MRP. We found that the expression of SKP2 was higher in HL-60/A cells than in HL-60 cells, but the expression of P27 kip1 was lower. The expression of SKP2 in HL-60/A cells nucleofected by SKP2 siRNA was down-regulated whereas the protein level of P27 kip1 was up-regulated. Compared with the MRP expression level in the control group (nucleofected by control siRNA), the mRNA and protein expression levels of MRP in HL-60/A cells nucleofected by SKP2 siRNA were lower, and the latter cells were more sensitive to adriamycin, daunorubicin, and arabinosylcytosine. Down-regulating the SKP2 expression and arresting cells in the G 0 /G 1 phase improve drug sensitivity of leukemia cells with down-regulated MRP expression.

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Section: Discussionmentioning

confidence: 99%

SKP2 siRNA inhibits the degradation of P27<sup>kip1</sup> and down-regulates the expression of MRP in HL-60/A cells

Xiao¹,

Su²,

Li³

et al. 2009

ABBS

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“…This is not the case of cisplatin, whose limited intracellular accumulation most often (although not always; see below) derives from reduced uptake (Smith et al, 1993;Wada et al, 1999;Baekelandt et al, 2000). Irrespective of the underlying mechanisms, several cisplatin-resistant cancer cells exhibit consistent reductions in the accumulation of cisplatin (Loh et al, 1992;Mellish et al, 1993).…”

Section: Mechanisms Of Pre-target Resistancementioning

confidence: 99%

Molecular mechanisms of cisplatin resistance

et al. 2011

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Platinum-based drugs, and in particular cis-diamminedichloroplatinum(II) (best known as cisplatin), are employed for the treatment of a wide array of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. Cisplatin exerts anticancer effects via multiple mechanisms, yet its most prominent (and best understood) mode of action involves the generation of DNA lesions followed by the activation of the DNA damage response and the induction of mitochondrial apoptosis. Despite a consistent rate of initial responses, cisplatin treatment often results in the development of chemoresistance, leading to therapeutic failure. An intense research has been conducted during the past 30 years and several mechanisms that account for the cisplatin-resistant phenotype of tumor cells have been described. Here, we provide a systematic discussion of these mechanism by classifying them in alterations (1) that involve steps preceding the binding of cisplatin to DNA (pre-target resistance), (2) that directly relate to DNAcisplatin adducts (on-target resistance), (3) concerning the lethal signaling pathway(s) elicited by cisplatin-mediated DNA damage (post-target resistance) and (4) affecting molecular circuitries that do not present obvious links with cisplatin-elicited signals (off-target resistance). As in some clinical settings cisplatin constitutes the major therapeutic option, the development of chemosensitization strategies constitute a goal with important clinical implications.

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“…3B). Because HL60/DOX does not express Pgp, but MRP, 12 and verapamil effect on HL60/ WT was slight, it is likely that verapamil inhibited the MRP-associated washout of 99m Tc- …”

Section: Discussionmentioning

confidence: 99%

“…It was demonstrated that HL60/DOX was 13-fold more resistant to doxorubicin than HL60/WT. 12 Both cell lines were cultured in RPMI-1640 medium (Nissui Seiyaku, Tokyo, Japan) supplemented with 10% heat-inactivated fetal calf serum (FCS; ICN, Aurora, OH) and 2 mM glutamine (Wako, Tokyo, Japan) at 37°C in 5% CO 2 / 95% air and 100% relative humidity. To obtain a pure cellular population of HL60/ DOX cells in terms of doxorubicin resistance, the cells were grown in the medium containing 100 nM doxorubicin (Kyowa, Tokyo, Japan), since sensitive cells did not survive at this concentration.…”

Section: Cell Culturementioning

confidence: 99%

Technetium-99m-Tetrofosmin Would Be a Substrate for Multidrug Resistance-associated Protein (MRP): Comparison between a Leukemia Cell Line with High MRP Gene Expression and Its Parental Cell Line

Kinuya

Yokoyama

et al. 2001

Cancer Biotherapy and Radiopharmaceuticals

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Selectively induced high MRP gene expression in multidrug-resistant human HL60 leukemia cells

Cited by 21 publications

References 31 publications

SKP2 siRNA inhibits the degradation of P27<sup>kip1</sup> and down-regulates the expression of MRP in HL-60/A cells

SKP2 siRNA inhibits the degradation of P27<sup>kip1</sup> and down-regulates the expression of MRP in HL-60/A cells

Molecular mechanisms of cisplatin resistance

Technetium-99m-Tetrofosmin Would Be a Substrate for Multidrug Resistance-associated Protein (MRP): Comparison between a Leukemia Cell Line with High MRP Gene Expression and Its Parental Cell Line

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Selectively induced high MRP gene expression in multidrug-resistant human HL60 leukemia cells

Cited by 21 publications

References 31 publications

SKP2 siRNA inhibits the degradation of P27&lt;sup&gt;kip1&lt;/sup&gt; and down-regulates the expression of MRP in HL-60/A cells

SKP2 siRNA inhibits the degradation of P27&lt;sup&gt;kip1&lt;/sup&gt; and down-regulates the expression of MRP in HL-60/A cells

Molecular mechanisms of cisplatin resistance

Technetium-99m-Tetrofosmin Would Be a Substrate for Multidrug Resistance-associated Protein (MRP): Comparison between a Leukemia Cell Line with High MRP Gene Expression and Its Parental Cell Line

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SKP2 siRNA inhibits the degradation of P27<sup>kip1</sup> and down-regulates the expression of MRP in HL-60/A cells

SKP2 siRNA inhibits the degradation of P27<sup>kip1</sup> and down-regulates the expression of MRP in HL-60/A cells