Cisplatin 顺铂
| EC | EINECS 239-733-8 |
| MDL | MFCD00011623 |
| 别名 | 顺二氯二氨基铂; ?顺氯氨铂; CIS-PLATIN |
| CAS | 15663-27-1 |
| 分子式 | Cl2H6N2Pt |
| 分子量 | 300.05 |
| 纯度 | HPLC≥98% |
| 单位 | 瓶 |
| 生物活性 | Cisplatin 是一种抗肿瘤化疗药物，它与 DNA 交联引起癌细胞中DNA损伤[1-4]。 |
| In Vitro | 顺铂（50μM）在肾近端小管细胞（RPTC）中产生时间依赖性细胞凋亡，导致细胞收缩，半胱天冬酶3活性增加50倍，磷脂酰丝氨酸外化增加4倍，增加5倍和15倍分别在染色质浓缩和DNA亚倍体中[2]。顺铂以剂量依赖性方式引起HeLa细胞的凋亡，浓度为30μM顺铂导致24小时处理后大于90％的细胞群死亡。使用30μM浓度检查顺铂诱导的细胞凋亡的动力学。顺铂激活MEK/ERK信号通路，20和30μM顺铂，两者均导致显著的细胞凋亡，导致ERK的强烈激活[1]。 |
| In Vivo | 在携带黑色素瘤的小鼠中，顺铂（4 mg/kg BW）可减小实体瘤的大小和重量，HemoHIM补充顺铂可增加肿瘤大小和体重的减少[3]。与对照大鼠相比，顺铂给药导致肾重量显著增加，占总体重，尿量，血清肌酐和血尿素氮的百分比分别为132,315,797和556％[4]。 |
| SMILES | [Cl-][Pt+2]([Cl-])([NH3])[NH3] |
| 靶点 | Ferroptosis;DNA Alkylator/Crosslinker |
| 动物实验 | 小鼠[3]将小鼠随机分成三组（对照组，顺铂和顺铂+ HemoHIM），每组由20只小鼠组成。在初始注射顺铂之前3天，将B16F0黑素瘤（5×10 5个细胞/小鼠）接种到小鼠的皮下股骨左侧区域。在第0,7和14天（总共三次注射）以4mg/kg体重（BW）腹膜内注射顺铂。实验组用HemoHIM插管，终浓度为100mg/kgB.W.每天从第-1天到第16天，而对照组仅接受水。在初始注射顺铂后第17天，分别对每组的所有小鼠进行实验，以评估肿瘤重量或肿瘤大小。肿瘤大小计算如下：肿瘤大小= ab2/2，其中a和b分别是更大和更小的直径。将体重为200-250g的大鼠[4]雄性Sprague-Dawley大鼠随机分成4组，每组4或5只动物。第一组（对照）接受用于辣椒素（Cap）的载体（5％羧甲基纤维素钠溶液（CMC-Na），5mL/kg体重，po）。第二组在5％CMC-Na（5 mL/kg）中接受Cap（10 mg/kg/d，po），第三组接受5％CMC-Na连续6天注射顺铂（5 mg/kg in生理盐水溶液，ip）。第四组在顺铂注射（5mg/kg，腹膜内注射）后连续6天在5％CMC-Na中接受Cap（10mg/kg/d，po）。对于所有团体，每天两次给予Cap或车辆。使用来自我们的初步实验的数据选择所选的帽浓度和剂量施用方案而不诱导任何大鼠肠损伤。 |
| 细胞实验 | 将HeLa和A549细胞维持在补充有10％胎牛血清，100单位青霉素和100μg链霉素/ mL的Dulbecco改良Eagle培养基中。将它们在37℃下在含有5％CO 2的加湿室中培养。为了诱导细胞凋亡，在顺铂（0-30μM）处理前1天将细胞接种在60-mm培养皿中[1]。 |
| 数据来源文献 | [1]. Wang X, et al. Requirement for ERK activation in cisplatin-induced apoptosis. J Biol Chem. 2000 Dec 15;275(50):39435-43. [2]. Cummings BS, et al. Cisplatin-induced renal cell apoptosis: caspase 3-dependent and -independent pathways. J Pharmacol Exp Ther. 2002 Jul;302(1):8-17. [3]. Park HR, et al. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice. BMC Cancer. 2009 Mar 17;9:85. [4]. Shimeda Y, et al. Protective effects of capsaicin against cisplatin-induced nephrotoxicity in rats. Biol Pharm Bull. 2005 Sep;28(9):1635-8. |
| 规格 | 20mg 100mg 200mg 500mg |
Cisplatin与 DNA 交联引起癌细胞中 DNA 损伤，可用于抗肿瘤化疗药物方向的研究。
使用本产品的应用案例：
文章：PD-1/PD-L1 enhanced cisplatin resistance in gastric cancer through PI3K/AKT mediated P-gp expression
作者：Lijun Wu 1, Shiyi Cai 1, Yiyun Deng 1, Zhe Zhang 1, Xiehai Zhou 2, Yong Su 3, Dujuan Xu 4
PMID: 33581579 DOI: 10.1016/j.intimp.2021.107443
Background: Programmed cell death receptor 1 (PD-1) is an immunosuppressive molecule expressed on T cells, and its ligand (PD-L1) which expressed on tumor cells play pivotal roles in regulating host immune responses. However, little is known whether PD-1/PD-L1 axis could directly activates intracellular oncogenic signaling pathways in tumor cells, leading to tumor resistance.
Methods: In the present study, the expression of PD-1 and PD-L1 in the tissues of gastric cancer was detected by western blot and immunofluorescence. The effect of PD-L1-Fc and cisplatin on resistant gastric cancer cells was examined by MTT assay and Flow Cytometry. In addition. The effect of PD-L1-Fc on the expression of P-gp in gastric cancer cells and resistant gastric cancer cells was detected by quantitative real-time reverse-transcription PCR (qRT-PCR) and western blot. The molecular mechanisms of the regulation of cisplatin and PD-L1-Fc treatment were evaluated by western blot.
Results: We found that the level of PD-1 was significantly increased in human gastric cancer tissues and drugresistant gastric cancer cells and P-gp was the same result. The PD-L1 could reduce the level of cell damage caused by cisplatin. In addition, we found PD-L1 can also up-regulate the expression of P-gp. Mechanistically, PD-L1 activated the PI3K/AKT signaling pathway in which PI3K/AKT pathway inhibition attenuated the upregulation of P-gp.
Conclusion: PD-1/PD-L1 enhanced cisplatin resistance in gastric cancer through PI3K/AKT mediated P-gp expression.