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PP2A inhibition with LB100 enhances cisplatin cytotoxicity and overcomes cisplatin resistance in medulloblastoma cells


, : PP2A inhibition with LB100 enhances cisplatin cytotoxicity and overcomes cisplatin resistance in medulloblastoma cells. Oncotarget 7(11): 12447-12463

The protein phosphatase 2A (PP2A) inhibitor, LB100, has been shown in pre-clinical studies to be an effective chemo- and radio-sensitizer for treatment of various cancers. We investigated effects associated with LB100 treatment alone and in combination with cisplatin for medulloblastoma (MB) in vitro and in vivo in an intracranial xenograft model. We demonstrated that LB100 had a potent effect on MB cells. By itself, LB100 inhibited proliferation and induced significant apoptosis in a range of pediatric MB cell lines. It also attenuated MB cell migration, a pre-requirement for invasion. When used in combination, LB100 enhanced cisplatin-mediated cytotoxic effects. Cell viability in the presence of 1 uM cisplatin alone was 61% (DAOY), 100% (D341), and 58% (D283), but decreased with the addition of 2 μM of LB100 to 26% (DAOY), 67% (D341), and 27% (D283), (p < 0.005). LB100 suppressed phosphorylation of the STAT3 protein and several STAT3 downstream targets. Also, LB100 directly increased cisplatin uptake and overcame cisplatin-resistance in vitro. Finally, LB100 exhibited potent in vivo anti-neoplastic activity in combination with cisplatin in an intracranial xenograft model.

US$19.90

PMID: 26799670

DOI: 10.18632/oncotarget.6970


Other references

Ohgi, K.; Kodaka, A.; Iwama, M.; Tsuji, T.; Irie, M.; Inokuchi, N.; Koyama, T., 2000: Modification of the base specificity of B2 base recognition site of RNase Rh by site-directed mutagenesis of Q32 and S93. Biochemical Society Transactions 28(5): A262, October

Seven, A.; Yuksel, B.; Kabil Kucur, S.; Yavuz, G.; Polat, M.; Unlu, B.S.; Keskin, N., 2016: The evaluation of hormonal and psychological parameters that affect bone mineral density in postmenopausal women. In this study we aimed to investigate the relationships between serum levels of DHEAS, reproductive hormones and low bone mineral density (BMD) in postmenopausal women. We also examined the relationship between psychological status of patients and...

Retief, E.; Herman, P.P.J., 1997: Strelitzia; Plants of the northern provinces of South Africa Keys and diagnostic characters. The four northern provinces of South Africa are North-West, Gauteng, Northern Province, and Mpumalanga, and the region extends from about 22 degrees 40 minutes to 32 degrees 0 minutes East and from 22 degrees 10 minutes to 28 degrees 0 minutes Sou...

D.A.B.lashov; A.V.R.coubratsky, 2011: Hypoxia tolerance of hybrids of carp Cyprinus carpio and golden carp Carassius auratus. Hypoxia tolerance of diploid gynogenetic and triploid backcross hybrids between golden carp <i>Carassius auratus</i> and carp <i>Cyprinus carpio</i> was investigated in comparison with carp. The more that heredity of golden...

Batrouni; Scalettar, 1992: World-line quantum Monte Carlo algorithm for a one-dimensional Bose model. Physical Review. B, Condensed Matter 46(14): 9051-9062

Donovan B.T., 1986: Scientific basis of psychiatry 2 hormones and human behavior. This volume of the series discusses hormones as they relate to psychiatry of the human. The various topics presented in the 12 main sections include the effects of the pituitary and the anterior pituitary gland, neurotransmitters and neuromodulato...

Li, D.; Liu, Y.; Pei, C.; Zhang, P.; Pan, L.; Xiao, J.; Meng, S.; Yuan, Z.; Bi, X., 2017: imiR-285- Yki/Mask double-negative feedback loop mediates blood-brain barrier integrity in iDrosophila. The Hippo signaling pathway is highly conserved from <i>Drosophila</i> to mammals and plays a central role in maintaining organ size and tissue homeostasis. The blood-brain barrier (BBB) physiologically isolates the brain from circulat...

Grecea Tarta A., 1969: Coleoptera larvae in the soil family carabidae. Studii si Cercetari de Biologie Seria Zoologie 21(4): 307-309

Henry J.M.; Jurgelski W., 1978: Ganglio gliomas of human central nervous system compared with chemically induced ganglio gliomas in the opossum. Journal of Neuropathology & Experimental Neurology 37(5): 626

Krämer, W.; Tülk, G.; Stopfkuchen, H., 1999: New fixation methods for orogastric feeding catheters in newborns and premature infants. Kinderkrankenschwester 18(2): 61-63