The Combination of BH3-Mimetic ABT-737 with the Alkylating Agent Temozolomide Induces Strong Synergistic Killing of Melanoma Cells Independent of p53
2011

Combining ABT-737 and Temozolomide to Treat Melanoma

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Author Information

Author(s): Steven N. Reuland, Nathaniel B. Goldstein, Katie A. Partyka, David A. Cooper, Mayumi Fujita, David A. Norris, Yiqun G. Shellman

Primary Institution: University of Colorado Denver, School of Medicine, Department of Dermatology

Hypothesis

Does the combination of BH3-mimetic ABT-737 with the alkylating agent Temozolomide induce stronger killing of melanoma cells independent of p53?

Conclusion

The combination of ABT-737 and Temozolomide significantly reduces tumor growth in melanoma cells and induces apoptosis through a p53-independent mechanism.

Supporting Evidence

  • The combination treatment drastically reduced tumor growth in a mouse model.
  • ABT-737 and Temozolomide together induced strong apoptosis in melanoma cell lines.
  • Noxa was significantly induced by the combination treatment, which was not observed with single drug treatments.

Takeaway

Using two drugs together can help kill melanoma cells better than using just one, even if the cells don't have a specific protein called p53.

Methodology

The study used in vitro assays on melanoma cell lines and a mouse xenograft model to assess the effects of ABT-737 and Temozolomide.

Limitations

The study primarily focused on specific melanoma cell lines and may not generalize to all melanoma types.

Statistical Information

P-Value

0.0005

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0024294

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