PURPOSE: bcl-2 and c-myc oncogenes are frequently overexpressed in different human tumors, including melanoma. Here, we evaluate the combined efficacy of two antisense oligonucleotides targeting bcl-2 mRNA (ODN bcl-2) and c-myc mRNA (ODN c-myc) in combination with cis-diammine dichloroplatinum (cisplatin, DDP) on three human melanoma lines (LM, NG, and M20). EXPERIMENTAL DESIGN: Two different sequences were designed to treat tumor-bearing mice: in the first one, ODN bcl-2 at a dose of 0.2 mg/day x4, followed by DDP given i.p. at a dose of 3.3 mg/kg/day x3 and ODN c-myc i.v. at 0.5 mg/day x7, whereas the other sequence consisted of ODN c-myc given as first agent followed by DDP and ODN bcl-2 at the same doses. Mice received three complete cycles of treatment in 1-week intervals. RESULTS: The treatment sequence with ODN bcl-2/DDP/ODN c-myc combination completely inhibited growth in NG tumor and induced a 35-day delay in LM tumor growth. In contrast, the M20 tumor growth was unaffected by the combination. A discrete amount of c-Myc and bcl-2 protein expression in both LM and NG tumors was detected, whereas no detectable levels of the two proteins were observed in M20 tumors. Compared with the other combination, the sequence (ODN bcl-2/DDP/ODN c-myc) produced the most effective results, producing a significant decrease in bcl-2 and c-Myc protein expression, which in turn significantly increased the survival of NG- and LM-bearing mice, with 4 mice out of 11 and 1 out of 7 mice being cured, respectively. Finally, this combination increased the apoptotic rate and produced an antiangiogenetic effect. CONCLUSIONS: These results show that an antisense approach to the treatment of melanoma xenografts overexpressing either bcl-2 or c-myc oncogenes represents a successful strategy to improve the response to chemotherapy in melanoma, with particular attention to the treatment sequence.
PURPOSE:bcl-2 and c-myc oncogenes are frequently overexpressed in different humantumors, including melanoma. Here, we evaluate the combined efficacy of two antisense oligonucleotides targeting bcl-2 mRNA (ODN bcl-2) and c-myc mRNA (ODN c-myc) in combination with cis-diammine dichloroplatinum (cisplatin, DDP) on three humanmelanoma lines (LM, NG, and M20). EXPERIMENTAL DESIGN: Two different sequences were designed to treat tumor-bearing mice: in the first one, ODN bcl-2 at a dose of 0.2 mg/day x4, followed by DDP given i.p. at a dose of 3.3 mg/kg/day x3 and ODN c-myc i.v. at 0.5 mg/day x7, whereas the other sequence consisted of ODN c-myc given as first agent followed by DDP and ODN bcl-2 at the same doses. Mice received three complete cycles of treatment in 1-week intervals. RESULTS: The treatment sequence with ODN bcl-2/DDP/ODN c-myc combination completely inhibited growth in NG tumor and induced a 35-day delay in LM tumor growth. In contrast, the M20 tumor growth was unaffected by the combination. A discrete amount of c-Myc and bcl-2 protein expression in both LM and NG tumors was detected, whereas no detectable levels of the two proteins were observed in M20 tumors. Compared with the other combination, the sequence (ODN bcl-2/DDP/ODN c-myc) produced the most effective results, producing a significant decrease in bcl-2 and c-Myc protein expression, which in turn significantly increased the survival of NG- and LM-bearing mice, with 4 mice out of 11 and 1 out of 7 mice being cured, respectively. Finally, this combination increased the apoptotic rate and produced an antiangiogenetic effect. CONCLUSIONS: These results show that an antisense approach to the treatment of melanoma xenografts overexpressing either bcl-2 or c-myc oncogenes represents a successful strategy to improve the response to chemotherapy in melanoma, with particular attention to the treatment sequence.
Authors: Constantin d'Ydewalle; Daniel M Ramos; Noah J Pyles; Shi-Yan Ng; Mariusz Gorz; Celeste M Pilato; Karen Ling; Lingling Kong; Amanda J Ward; Lee L Rubin; Frank Rigo; C Frank Bennett; Charlotte J Sumner Journal: Neuron Date: 2016-12-22 Impact factor: 17.173
Authors: Paola Matarrese; Barbara Ascione; Laura Ciarlo; Rosa Vona; Carlo Leonetti; Marco Scarsella; Anna M Mileo; Caterina Catricalà; Marco G Paggi; Walter Malorni Journal: Mol Cancer Date: 2010-08-04 Impact factor: 27.401
Authors: Enrico P Spugnini; Annamaria Biroccio; Roberta De Mori; Marco Scarsella; Carmen D'Angelo; Alfonso Baldi; Carlo Leonetti Journal: J Transl Med Date: 2011-07-28 Impact factor: 5.531
Authors: Véronique Mathieu; Christine Pirker; Elisabeth Martin de Lassalle; Mathieu Vernier; Tatjana Mijatovic; Nancy DeNeve; Jean-François Gaussin; Mischael Dehoux; Florence Lefranc; Walter Berger; Robert Kiss Journal: J Cell Mol Med Date: 2009-02-20 Impact factor: 5.310