Oxaliplatin CAS 61825-94-3

On cancer cell chromosomal DNA, but its complexes can also be formed in nucleosomes. In cells, oxaliplatin induces three types of cross-linking.

• Intra-strand cross-linking of DNA
  Intra-strand crosslinking of DNA means that in base pairing, two G bases form pairings, or less frequently form G-A base pairs instead of normal G-C pairings. Meanwhile, intra-strand cross-linking of DNA appears to be the main mechanism for inducing DNA damage.
• Cross-linking of DNA strands
  DNA strand crosslinking is thought to be of great importance in the cytotoxicity of cisplatin. DNA cross-linking appears to be less important in the anticancer mechanism of oxaliplatin.
• DNA-protein cross-linking
  As for DNA-protein cross-linking, although it can denature enzymes and other important proteins in cells, current research has not demonstrated that it can cause cell death.

Oxaliplatin can inhibit DNA synthesis because it is an inhibitor of thymidine synthase itself. Many studies have found that when oxaliplatin and fluorouracil are combined with fluorouracil, the intracellular thymidine synthase is lower than that of single drug. The specific mechanism Not yet known.

There are three mechanisms by which oxaliplatin inhibits RNA transcription:

• Binding to transcription factors
  During the initiation stage of transcription, platinum-DNA complexes can act as binding sites for transcription factors, thereby preventing the normal binding of transcription factors to promoters.
• Inhibit RNA polymerase
  Cisplatin can form a complex with some polymerases (such as polymerase II), so that the enzyme cannot enter its active site, thereby inhibiting its action. Oxaliplatin should also have this effect.
• Involvement in the mechanism of nucleosome-histone-DNA complexes
  Nucleosomal histone-DNA complexes affect the binding of DNA strands to RNA polymerase to prevent its transcription, and oxaliplatin enhances this pathway.

Both animal tumor models and human experiments have found that oxaliplatin can lead to immune death of tumors. After induction of colon cancer in mice, oxaliplatin treatment showed that colon cancer cells send out several immunological signals on their surface before apoptosis. These signals are the product of interferon gamma in T cells and can interact with dendritic cells. Receptor 4 interaction.

The reason for this phenomenon is currently speculated to be that oxaliplatin causes the body’s immune system to respond, thereby secreting anti-tumor antibodies. This is because in animal models deficient in dendritic cell receptor 4 and colon cancer patients, despite oxaliplatin infusion, the immune signal described above was not observed, and these patients had shorter disease-free periods and better overall survival. low, the results were statistically significant.