Oxaliplatin

The main mechanism of action of Oxaliplatin is mediated through the formation of DNA–adducts. Oxaliplatin induces primary and secondary DNA lesions that lead to cell apoptosis. ^[1] Oxaliplatin is active against human melanoma cell lines C32 and G361 with IC50 of 0.98 mM and 0.14 mM, respectively. ^[2] Oxaliplatin effectively inhibits bladder carcinoma cell lines RT4 and TCCSUP, ovarian carcinoma cell line A2780, colon carcinoma cell line HT-29, glioblastoma cell lines U-373MG and U-87MG, and melanoma cell lines SK-MEL-2 and HT-144 with IC50 of 11 μM, 15 μM, 0.17 μM, 0.97 μM, 2.95 μM, 17.6 μM, 30.9 μM and 7.85 μM, respectively. ^[4]

The cytotoxicity studies are carried out with the sulforhodamine-B microculture colorimetrie assay. Typically, cells are plated into 96-well plates on day 0 and exposed to Oxaliplatin on day 1; the sulforhodamine-B assay is carried out 48 h after Oxaliplatin exposure. The plates are incubated at 37 °C in 5% CO₂ and 100% relative humidity at all times except when adding Oxaliplatin and during the final assay period. The initial number of cells plated for the assay ranged from 2-20 × 10³ cells/50 /nL/well. The numbers of cells for plating and the drug exposure time are based on pilot studies using the criteria that (a) the cells in control wells are still in the log phase of growth on the day of the assay; (b) the maximum absorbance for the untreated controls on the day of the assay is in the range of 1.0 to 1.5; and (c) cells go through >2 doublings during the drug exposure. Eight wells are used per concentration. The plates are read at 570 and/or 540 nm using a Biotek Instruments model EL309 microplate reader interfaced with an IBM PC-compatible computer. The data are transferred and transformed into a LOTUS 1-2-3 format by the computer program DATALOG, and survival fractions are calculated by comparing the drug treated with control

A weekly i.p. injection of Oxaliplatin at 10 mg/kg to nude mice bearing hepatocellular HCCLM3 tumors significantly reduces tumor volume and apoptotic index. ^[6] Oxaliplatin (5mg/kg, i.v. on days 1, 5 and 9) is active on T-leukemia-lymphoma L40 AKR with T/C of 1.77. Oxaliplatin is also efficient on intracerebrally grafted L1210 leukemia, MA 16-C xenografts, B16 melanoma xenografts, Lewis lung xenografts and C₂₆ colon carcinoma xenografts. ^[7] Oxaliplatin induces impairment of retrograde neuronal transport in mice. ^[8]