Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxaliplatin (L-OHP), a diaminocyclohexane platinum derivative, is an active and well tolerated anticancer drug which is presently used in the treatment of gastrointestinal tumours. Since the efficacy of L-OHP in the treatment of multiple myeloma (MM) has not yet been evaluated, we studied the antiproliferative activity of this compound in vitro in a panel of MM cell lines (XG1, XG1a, U266 and IM-9). We found that L-OHP inhibited the growth of MM cells at therapeutically achievable concentrations (IC(50): 5-10 microM after 24 h of exposure) and was more active than Cisplatin (CDDP) or Carboplatin (CBDCA). The activity of L-OHP was apparently not affected by interleukin-6 (IL-6), the major growth and survival factor of MM cells. We also found that L-OHP induced apoptotic cell death. We demonstrated that the combination of L-OHP with Dexamethasone (Dex) resulted in the enhancement of the anti-myeloma effects. L-OHP and Dex both induced poly adenosine diphosphate (ADP)-ribose polymerase (PARP) cleavage and this induction was enhanced by the combined treatment. L-OHP-induced apoptosis correlated with caspase-3 cleavage, but this correlation could not be demonstrated in Dex-treated cells. Taken together, these in vitro results provide a rationale for the experimental use of L-OHP in the treatment of MM patients and suggest therapeutic combinations of potential value.
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PMID:Oxaliplatin (L-OHP) treatment of human myeloma cells induces in vitro growth inhibition and apoptotic cell death. 1200 4

This study was aimed to investigate the effects of oxaliplatin on human multiple myeloma cell line RPMI-8226 and its mechanism. The proliferation inhibitory rate of RPMI8226 cells was assayed by MTT, the morphological changes of RPMI-8226 cells were observed by inverted fluorescent microscopy and transmission electron microscopy, the apoptosis rate and the cell cycle distribution of RPMI-8226 cells were detected by flow cytometry, The effects of oxaliplatin on the expression of Bcl-2, caspase-8, caspase-3 mRNA were tested by RT-PCR, Bcl-2 protein expression of RPMI-8226 cells was analyzed by Western blot. The results showed that oxaliplatin could inhibit the proliferation of RPMI-8226 cells in time and dose-dependent manners. Cell number in oxaliplatin group was significantly less than that in control group under light microscope, and the growth arrangement was irregular, apoptotic cells could be seen. Under electron microscope, typical apoptotic morphological and ultrastructural changes could be observed. Flow cytometry results showed that oxaliplatin could induce apoptosis of RPMI-8226 cells, the difference have statistical significance (P < 0.05). Oxaliplatin mainly arrested RPMI-8226 cells in the S phase (P < 0.05). The expression of Bcl-2 mRNA did not have apparent change, while the expression of caspase-8, caspase-3 mRNA increased (P < 0.05). Western blot results suggested that the expression of Bcl-2 protein had no obvious change. It is concluded that the oxaliplatin can induce apoptosis of RPMI-8226 cells, activating the death receptor pathway and arresting cell cycle may be two of the related mechanisms, Bcl-2 gene has unobservable effects in the process of oxaliplatin-induced cell apoptosis.
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PMID:[Mechanisms of oxaliplatin-induced apoptosis of human multiple myeloma cell RPMI8226]. 2348