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RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells.

Zhang H, Zhang S, He H, Zhang C, Chen Y, Yu D, Chen J, Shao R - Acta Pharm Sin B (2014)

Bottom Line: This synergistic effect was associated with the inhibitions of phospho-AKT, phospho-ERK and NF-κB.In mouse colon tumor CT26 animal models, GAP159 combined with CDDP significantly suppressed CT26 tumor growth, and GAP159 alone showed slight inhibitory effect.Our data suggests that co-treatment of GAP159 and chemotherapeutics will become a potential therapeutic strategy for colon cancers.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

ABSTRACT
To increase the efficacy of currently used anti-cancer genotoxins, one of the current efforts is to find agents that can sensitize cancer cells to genotoxins so that the efficacious doses of genotoxins can be lowered to reduce deleterious side-effects. In this study, we reported that a synthetic RasGAP-derived peptide GAP159 could enhance the effect of chemotherapeutic agent cisplatin (CDDP) in human colon carcinoma HCT116 cells. Our results showed that GAP159 significantly increased the CDDP-induced cytotoxicity and apoptosis in HCT116 cells. This synergistic effect was associated with the inhibitions of phospho-AKT, phospho-ERK and NF-κB. In mouse colon tumor CT26 animal models, GAP159 combined with CDDP significantly suppressed CT26 tumor growth, and GAP159 alone showed slight inhibitory effect. Our data suggests that co-treatment of GAP159 and chemotherapeutics will become a potential therapeutic strategy for colon cancers.

No MeSH data available.


Related in: MedlinePlus

GAP159 inhibits HCT116 cell growth. A: GAP159 synergistically enhanced the inhibitory effects of CDDP on HCT116 cells (#P<0.05 vs CDDP); B: CDI value of co-treatment of GAP159 and CDDP.
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f0010: GAP159 inhibits HCT116 cell growth. A: GAP159 synergistically enhanced the inhibitory effects of CDDP on HCT116 cells (#P<0.05 vs CDDP); B: CDI value of co-treatment of GAP159 and CDDP.

Mentions: To explore whether GAP159 might be a potential therapeutic agent against HCT116 cells, we investigated the anti-proliferative activity of GAP159 with or without CDDP. After drug exposure, cell proliferation was determined by MTT assay (Fig. 2A). GAP159 alone inhibited proliferation of HCT116 cells in a dose and time-dependent manner. For 48 h treatment, the inhibition rates of 10 μmol/L and 30 μmol/L GAP159 were 21.3% and 46.34%, respectively. When treated the cells with 30 μmol/L GAP159, the inhibition rates of 24, 48 and 72 h treatment were 39.33%, 46.34%, 54.46%, respectively. The combination of GAP159 and CDDP showed significant anti-proliferative effects on HCT116 cells as compared with GAP159 or CDDP alone (P<0.05). For 72 h treatment, the inhibitory rates of 10 μmol/L and 30 μmol/L GAP159 combined with CDDP were 78.83% and 88.33%, respectively.


RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells.

Zhang H, Zhang S, He H, Zhang C, Chen Y, Yu D, Chen J, Shao R - Acta Pharm Sin B (2014)

GAP159 inhibits HCT116 cell growth. A: GAP159 synergistically enhanced the inhibitory effects of CDDP on HCT116 cells (#P<0.05 vs CDDP); B: CDI value of co-treatment of GAP159 and CDDP.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590723&req=5

f0010: GAP159 inhibits HCT116 cell growth. A: GAP159 synergistically enhanced the inhibitory effects of CDDP on HCT116 cells (#P<0.05 vs CDDP); B: CDI value of co-treatment of GAP159 and CDDP.
Mentions: To explore whether GAP159 might be a potential therapeutic agent against HCT116 cells, we investigated the anti-proliferative activity of GAP159 with or without CDDP. After drug exposure, cell proliferation was determined by MTT assay (Fig. 2A). GAP159 alone inhibited proliferation of HCT116 cells in a dose and time-dependent manner. For 48 h treatment, the inhibition rates of 10 μmol/L and 30 μmol/L GAP159 were 21.3% and 46.34%, respectively. When treated the cells with 30 μmol/L GAP159, the inhibition rates of 24, 48 and 72 h treatment were 39.33%, 46.34%, 54.46%, respectively. The combination of GAP159 and CDDP showed significant anti-proliferative effects on HCT116 cells as compared with GAP159 or CDDP alone (P<0.05). For 72 h treatment, the inhibitory rates of 10 μmol/L and 30 μmol/L GAP159 combined with CDDP were 78.83% and 88.33%, respectively.

Bottom Line: This synergistic effect was associated with the inhibitions of phospho-AKT, phospho-ERK and NF-κB.In mouse colon tumor CT26 animal models, GAP159 combined with CDDP significantly suppressed CT26 tumor growth, and GAP159 alone showed slight inhibitory effect.Our data suggests that co-treatment of GAP159 and chemotherapeutics will become a potential therapeutic strategy for colon cancers.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

ABSTRACT
To increase the efficacy of currently used anti-cancer genotoxins, one of the current efforts is to find agents that can sensitize cancer cells to genotoxins so that the efficacious doses of genotoxins can be lowered to reduce deleterious side-effects. In this study, we reported that a synthetic RasGAP-derived peptide GAP159 could enhance the effect of chemotherapeutic agent cisplatin (CDDP) in human colon carcinoma HCT116 cells. Our results showed that GAP159 significantly increased the CDDP-induced cytotoxicity and apoptosis in HCT116 cells. This synergistic effect was associated with the inhibitions of phospho-AKT, phospho-ERK and NF-κB. In mouse colon tumor CT26 animal models, GAP159 combined with CDDP significantly suppressed CT26 tumor growth, and GAP159 alone showed slight inhibitory effect. Our data suggests that co-treatment of GAP159 and chemotherapeutics will become a potential therapeutic strategy for colon cancers.

No MeSH data available.


Related in: MedlinePlus