Cisplatin 是一种 DNA 交联剂，能够通过在癌细胞中形成 DNA 加合物来抑制 DNA 合成。它可激活铁死亡并诱导自噬。

Cisplatin, a DNA-crosslinking agent, is able to suppress DNA synthesis by conforming DNA adducts in cancer cells.

Cisplatin (50 μM) produced time-dependent apoptosis in RPTCs, causing cell shrinkage, a 50-fold increase in caspase 3 activity, a 4-fold increase in phosphatidylserine externalization, and 5- and 15-fold increases in chromatin condensation and DNA hypoploidy, respectively. Mitochondrial membrane potential and ATP levels did not change at any time during cisplatin exposure [1]. High concentrations of cisplatin (800 μM) led to necrotic cell death over a few hours. Much lower concentrations of cisplatin (8 microM) led to apoptosis, which caused loss of the cell monolayer over several days. DNA electrophoresis of cells exposed to 800 μM cisplatin yielded a "smear" pattern, due to random DNA degradation [2].

In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size and weight. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-gamma secretion from splenocytes [3]. The maximum tolerated dose of cisplatin given weekly i.v. x 2 induced a tumor growth inhibition (GI) of 77.5% and 85.1% of the serous xenografts Ov.Ri(C) and OVCAR-3, respectively. The mucinous xenograft Ov.Pe was relatively resistant to cisplatin. The maximum tolerated dose of CTX, given i.p. x 2 with a 2-week interval, induced a GI between 52.9% and 59.7% for each of the 3 xenografts [4].

Rabbit renal proximal tubules were isolated using the iron oxide perfusion method and grown in 35-mm tissue culture dishes under improved conditions as described previously. The cell culture medium was a 1:1 mixture of Dulbecco's modified Eagle's medium/Ham's F-12 (without D-glucose, phenol red, or sodium pyruvate) supplemented with 15 mM HEPES buffer, 2.5 mM L-glutamine, 1 μM pyridoxine HCl, 15 mM sodium bicarbonate, and 6 mM lactate. Hydrocortisone (50 nM), selenium (5 ng/ml), human transferrin (5 μg/ml), bovine insulin (10 nM), and L-ascorbic acid-2-phosphate (50 μM) were added to fresh culture medium immediately before daily media change. In general, confluent RPTCs were treated with inhibitors or diluent control [typically DMSO at 0.1% (v/v)] for 30 min before treatment with cisplatin. Aliquots of RPTCs were used for various assays as detailed below [1].

Mice were divided randomly into three groups (Control, Cisplatin and Cisplatin+HemoHIM), and each group consisted of twenty mice. B16F0 melanoma (5 × 10^5 cells/mouse) was inoculated into subcutaneous femoral left region of mice at 3 days before an initial injection of cisplatin. Cisplatin was injected intraperitoneally at 4 mg/kg body weight (B.W.) on day 0, 7 and 14 (total three injections). Experimental group was intubated with HemoHIM at a final concentration of 100 mg/kgB.W. by everyday from day -1 to day 16, while the control group received only water. On day 17 after initial injection of cisplatin, all mice of each group were experimented, respectively, to evaluate tumor weight or tumor size. The tumor size was calculated as follows: tumor size = ab^2/2, where a and b are the larger and smaller diameters, respectively [3].

15663-27-1

Cl2H6N2Pt

300.05

CDDP;cis-Diaminodichloroplatinum;顺铂

DMF:3 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years