Effect of reactivity on cellular accumulation and cytotoxicity of oxaliplatin analogues
Effect of reactivity on cellular accumulation and cytotoxicity of oxaliplatin analogues
复制标题
反应活性对奥沙利铂类似物细胞积累和细胞毒性的影响
DOI：
10.1007/s00775-012-0889-9
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
U. Jaehde
中科院分区：
文献类型：
--
作者：
I. Buss;Ganna V. Kalayda;A. Lindauer;Michael R. Reithofer;M. Galanski;B. Keppler;U. Jaehde
本研究旨在系统研究一组具有不同离去基团的奥沙利铂类似物在人癌细胞中的反应性、细胞蓄积和细胞毒性之间的关系。用毛细管电泳法研究了配合物对核苷酸2′-脱氧鸟苷5′-单磷酸和2′-脱氧腺苷5′-单磷酸的反应性。在奥沙利铂敏感和奥沙利铂耐药回盲部结直肠腺癌细胞系对（HCT-8/HCT-8 ox）中测量细胞蓄积和细胞毒性。铂浓度通过无火焰原子吸收光谱法测定。使用3-（4，5-二甲基噻唑-2-基）-2，5-二苯基-2H-溴化四唑（MTT）测定来评估细胞毒性。早期细胞铂积累主要受亲脂性的影响。在研究的四种铂络合物中，观察到三种铂络合物的反应性与细胞蓄积之间的关系，而最亲脂的奥沙利铂类似物是一个例外。反应性增加和亲脂性降低与高细胞毒活性相关。耐药性受亲脂性影响，但不受反应性影响。所观察到的关系可能有助于在奥沙利铂敏感以及奥沙利铂耐药细胞中具有高抗肿瘤活性的类似物的设计。
The purpose of this study was to systematically investigate the relationships between reactivity, cellular accumulation, and cytotoxicity of a panel of oxaliplatin analogues with different leaving groups in human carcinoma cells. The reactivity of the complexes towards the nucleotides 2′-deoxyguanosine 5′-monophosphate and 2′-deoxyadenosine 5′-monophosphate was studied using capillary electrophoresis. Cellular accumulation and cytotoxicity were measured in an oxaliplatin-sensitive and oxaliplatin-resistant ileocecal colorectal adenocarcinoma cell line pair (HCT-8/HCT-8ox). Platinum concentrations were determined by flameless atomic absorption spectrometry. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess cytotoxicity. Early cellular platinum accumulation was predominantly affected by lipophilicity. A relationship between reactivity and cellular accumulation was observed for three of four platinum complexes investigated, whereas the most lipophilic oxaliplatin analogue was an exception. Increased reactivity and reduced lipophilicity were associated with high cytotoxic activity. Resistance was influenced by lipophilicity but not by reactivity. The observed relationships may help in the design of analogues with high antitumoral activity in oxaliplatin-sensitive as well as oxaliplatin-resistant cells.
影响因子：
11.2
作者：
M. Alley;Dominic A. Scudiere;A. Monks;M. Hursey;M. Czerwiński;D. Fine;B. Abbott;J. Mayo;R. Sh
通讯作者：
M. Alley;Dominic A. Scudiere;A. Monks;M. Hursey;M. Czerwiński;D. Fine;B. Abbott;J. Mayo;R. Sh
影响因子：
11.2
作者：
Zhang, Shuzhong;Lovejoy, Katherine S.;Giacomini, Kathleen M.
通讯作者：
Giacomini, Kathleen M.
1,2-二氨基环己烷铂(IV)配合物的合成及其抗肿瘤活性。
影响因子：
3.9
作者：
Khokhar,AR;al-Baker,S;Siddik,ZH
通讯作者：
Siddik,ZH