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Chemosensitivity of glioblastoma cells during treatment with the organo-tin compound triethyltin(IV)lupinylsulfide hydrochloride.

作者信息

Barbieri Federica, Sparatore Fabio, Bonavia Rudy, Bruzzo Cristina, Schettini Gennaro, Alama Angela

机构信息

Laboratory of Pharmacology and Neuroscience, National Institute for Cancer Research, Advanced Biotechnology Center, Genoa, Italy.

出版信息

J Neurooncol. 2002 Nov;60(2):109-16. doi: 10.1023/a:1020630214549.

DOI:10.1023/a:1020630214549
PMID:12635657
Abstract

Malignant gliomas are the most common primary brain tumors in humans. However, poor response to conventional therapeutic approaches, including chemotherapy, leads invariably to disease recurrence and progression. The organo-tin derivative triethyltin(IV)lupinylsulfide hydrochloride (IST-FS 29) was identified and developed as potential antiproliferative agent in human cancer cell lines. However, for its peculiar chemical structure and good lipophilicity, this compound also appeared an eligible candidate for the treatment of gliobastoma cells. The present experiments were designed to explore the in vitro effects of IST-FS 29 on four human glioblastoma cell lines: A-172, DBTRG.05MG, U-87MG and CAS-1. The average IC50 values were obtained by MTT assay and ranged between 3 and 10 microM. Time-course assays with cell recovery after drug withdrawal, demonstrated marked cytotoxicity following exposure to IST-FS 29 for 8, 24 and 72 h. Cultures treated for 8 h were able to partially re-grow by 144 h; on the contrary, longer times of exposure did not allow surviving cells to recover from the damage and actively proliferate. Cell morphology of cultures exposed to IST-FS 29 was assessed by inverted light microscopy after 24 and 72 h and was more consistent with cell death by necrosis which included cell size reduction, vacuolation of cytoplasm, round dying cells. The present results and our previous data, in vitro and in vivo, indicate the relevant cytotoxic activity of this organo-tin compound and suggest that IST-FS 29 might be a promising novel agent to be developed for the treatment of malignant brain neoplasms.

摘要

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引用本文的文献

1
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本文引用的文献

1
Antitumor activity of a new orally active organotin compound: a preliminary study in murine tumor models.一种新型口服活性有机锡化合物的抗肿瘤活性:在小鼠肿瘤模型中的初步研究
Anticancer Drugs. 2002 Jul;13(6):599-604. doi: 10.1097/00001813-200207000-00006.
2
Pharmacotherapy of malignant astrocytomas of children and adults: current strategies and future trends.儿童与成人恶性星形细胞瘤的药物治疗:当前策略与未来趋势
CNS Drugs. 2001;15(9):719-43. doi: 10.2165/00023210-200115090-00005.
3
Antiproliferative activity and interactions with cell-cycle related proteins of the organotin compound triethyltin(IV)lupinylsulfide hydrochloride.
有机锡化合物盐酸三乙基锡(IV)羽扇豆硫醚的抗增殖活性及其与细胞周期相关蛋白的相互作用。
Chem Biol Interact. 2001 Mar 14;134(1):27-39. doi: 10.1016/s0009-2797(00)00249-0.
4
Expression of multidrug resistance-associated protein (MRP) in human gliomas.多药耐药相关蛋白(MRP)在人脑胶质瘤中的表达。
J Neurooncol. 2000 Sep;49(2):105-15. doi: 10.1023/a:1026528926482.
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Biology and treatment of malignant glioma.恶性胶质瘤的生物学特性与治疗
Semin Oncol. 2000 Jun;27(3 Suppl 6):1-10.
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Cytotoxicity in vitro and preliminary antitumor activity in vivo of a novel organotin compound.
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J Cancer Res Clin Oncol. 1999 Aug-Sep;125(8-9):481-6. doi: 10.1007/s004320050305.
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Cancer Treat Rev. 1999 Apr;25(2):83-101. doi: 10.1053/ctrv.1998.0107.
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Comparative molecular genetic profiles of anaplastic astrocytomas/glioblastomas multiforme and their subsequent recurrences.间变性星形细胞瘤/多形性胶质母细胞瘤及其后续复发的比较分子遗传学图谱。
Oncogene. 1999 Feb 11;18(6):1385-90. doi: 10.1038/sj.onc.1202440.