Cisplatin|15663-27-1|安捷凯

Background

Cisplatin is one of the best and first metal-based chemotherapeutic drugs, which is used for wide range of solid cancers such as testicular, ovarian, bladder, lung, cervical, head and neck cancer, gastric cancer and some other cancers. Studies confirmed that cisplatin exerts its anticancer activity by attacking more than one place. Cisplatin generally binds with genomic DNA (gDNA) or mitochondrial DNA (mtDNA) to create DNA lesions, block the production of DNA, mRNA and proteins, arrest DNA replication, activate several transduction pathways which finally led to necrosis or apoptosis.^[1]

In vitro and in vivo experiments indicated that cisplatin induced cell resistance and cisplatin administrated rats exhibited increased creatinine, urea, and uric acid and this effect was more pronounced than in rats treated with gentamicin.^[1]^[2]

参考文献:
[1]. Stordal B, et al. Understanding cisplatin resistance using cellular models. IUBMB Life. 2007 Nov;59(11):696-9.
[2]. Abouzed TK, et al. Assessment of gentamicin and cisplatin-induced kidney damage mediated via necrotic and apoptosis genes in albino rats. BMC Vet Res. 2021 Nov 16;17(1):350.

顺铂是最好的、最早的基于金属的化疗药物之一,用于治疗广泛的实体癌症,如睾丸癌、卵巢癌、膀胱癌、肺癌、宫颈癌、头颈部肿瘤和胃癌等。研究证实,顺铂通过攻击多个位置发挥其抗癌活性。通常情况下,顺铂与基因组DNA（gDNA）或线粒体DNA（mtDNA）结合形成DNA损伤,阻止DNA、mRNA和蛋白质的产生,阻滞DNA复制,并激活几条信号转导途径,最终导致坏死或凋亡。^[1]

体外和体内实验表明,顺铂会导致细胞耐药性增强,给予顺铂的大鼠显示出肌酐、尿素和尿酸水平升高的现象,而这种影响比使用庆大霉素治疗的大鼠更为显著。

Protocol

Cell experiment [1]:

Cell lines

H69 SCLC cells

Reaction Conditions

H69 SCLC cells were treated with100 ng/ml cisplatin, to produce the H69-CP or 200 ng/ml cisplatin to obtain the H69CIS200 cells. These doses are below an IC50 for cisplatin and are within the range achieved in the clinical use of cisplatin.

Applications

The cells were 2- to 4-fold resistant to cisplatin, which could be used to further study the resistance mechanism.

Animal experiment [2]:

Animal models

Adult male Wistar rats, weighing 160-200?g

Preparation Method

The rats were kept at 25?°C on a 12/12?h light/dark cycle, in single plastic cages with bedding, with access to standard rat food and water ad libitum. Rats were randomly assigned to one of three groups: 1) Control group, who received no intervention and maintained a regular diet; 2) Gentamicin group, who were administered 100?mg/kg BW IP gentamicin daily for 7?days; 3) Cisplatin group, who were administered 1.5?mg/kg BW IP cisplatin twice a week for 3 weeks.

Dosage form

1.5?mg/kg

Applications

Cisplatin and gentamicin could significantly elevate serum levels of creatinine, uric acid, and urea, with cisplatin showing higher elevation. Cisplatin could also significantly decrease the GSH and GPx levels.

参考文献:

[1]. Stordal B, et al. Understanding cisplatin resistance using cellular models. IUBMB Life. 2007 Nov;59(11):696-9.

[2]. Abouzed TK, et al. Assessment of gentamicin and cisplatin-induced kidney damage mediated via necrotic and apoptosis genes in albino rats. BMC Vet Res. 2021 Nov 16;17(1):350.