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Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines.

Zou Z, Xie L, Wei J, Yu L, Qian X, Chen J, Wang T, Liu B - BMC Complement Altern Med (2012)

Bottom Line: Median effect analysis was applied for determination of synergism and antagonism.Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines.Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University, China.

ABSTRACT

Background: Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death.

Methods: MTT assay was used to determine IC(50) values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI) method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI) double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results: Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells.

Conclusions: Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.

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Related in: MedlinePlus

GA down-regulates the expression of genes involved in Doc sensitivity. The mRNA expression of genes involved in Doc sensitivity, including β-tubulin III, tau and survivin, in BGC-823 cells was determined by qRT-PCR after 48 h of GA (0.25 μM) treatment. The mRNA expression of target genes was normalized to a control. *P < 0.01 compared with control. Data were quantified from three independent experiments.
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Figure 5: GA down-regulates the expression of genes involved in Doc sensitivity. The mRNA expression of genes involved in Doc sensitivity, including β-tubulin III, tau and survivin, in BGC-823 cells was determined by qRT-PCR after 48 h of GA (0.25 μM) treatment. The mRNA expression of target genes was normalized to a control. *P < 0.01 compared with control. Data were quantified from three independent experiments.

Mentions: Accumulating evidence indicates that various cellular proteins that are associated with microtubules can determine the sensitivity of cancer cells to microtubule-targeting agents and play a role in tumor cell resistance to these agents [13]. To explore the potential mechanism by which GA plus Doc induces apoptotic cell death, the expression of genes involved in Doc sensitivity that regulate microtubules, such as class III β-tubulin (β-tubulin III) and tau, were evaluated by qRT-PCR. It should be noted that 48 h of GA (0.25 μM) incubation markedly down-regulated the expression of β-tubulin III and tau (Figure 5). Moreover, the expression of survivin, which is recognized as an apoptosis inhibitor, [14] was also suppressed by GA administration (Figure 5). These results imply that β-tubulin III, tau and survivin might be involved in the GA-mediated anti-tumor effect.


Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines.

Zou Z, Xie L, Wei J, Yu L, Qian X, Chen J, Wang T, Liu B - BMC Complement Altern Med (2012)

GA down-regulates the expression of genes involved in Doc sensitivity. The mRNA expression of genes involved in Doc sensitivity, including β-tubulin III, tau and survivin, in BGC-823 cells was determined by qRT-PCR after 48 h of GA (0.25 μM) treatment. The mRNA expression of target genes was normalized to a control. *P < 0.01 compared with control. Data were quantified from three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3403986&req=5

Figure 5: GA down-regulates the expression of genes involved in Doc sensitivity. The mRNA expression of genes involved in Doc sensitivity, including β-tubulin III, tau and survivin, in BGC-823 cells was determined by qRT-PCR after 48 h of GA (0.25 μM) treatment. The mRNA expression of target genes was normalized to a control. *P < 0.01 compared with control. Data were quantified from three independent experiments.
Mentions: Accumulating evidence indicates that various cellular proteins that are associated with microtubules can determine the sensitivity of cancer cells to microtubule-targeting agents and play a role in tumor cell resistance to these agents [13]. To explore the potential mechanism by which GA plus Doc induces apoptotic cell death, the expression of genes involved in Doc sensitivity that regulate microtubules, such as class III β-tubulin (β-tubulin III) and tau, were evaluated by qRT-PCR. It should be noted that 48 h of GA (0.25 μM) incubation markedly down-regulated the expression of β-tubulin III and tau (Figure 5). Moreover, the expression of survivin, which is recognized as an apoptosis inhibitor, [14] was also suppressed by GA administration (Figure 5). These results imply that β-tubulin III, tau and survivin might be involved in the GA-mediated anti-tumor effect.

Bottom Line: Median effect analysis was applied for determination of synergism and antagonism.Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines.Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University, China.

ABSTRACT

Background: Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death.

Methods: MTT assay was used to determine IC(50) values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI) method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI) double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results: Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells.

Conclusions: Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.

Show MeSH
Related in: MedlinePlus