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Table 3 Effects of combining Nutlin-3a with chemotherapy

From: MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines

A

       

Combination Index

Drug combination with Nutlin-3a

 

OSA

T778

U2OS

  

CI ± SE

 

CI ± SE

 

CI ± SE

 

Dox

1:1

1,2 ± 0,3

antagonism

0,7 ± 0,2

synergy

1,1 ± 0,2

antagonism

 

1:2

1,0 ± 0,1

additivity

1,4 ± 0,4

antagonism

2,1 ± 0,7

antagonism

 

2:1

0,8 ± 0,1

synergy

0,9 ± 0,2

synergy

1,7 ± 0,6

antagonism

Cis

1:1

1,9 ± 0,6

antagonism

1,2 ± 0,2

antagonism

1,4 ± 0,3

antagonism

 

1:2

2,1 ± 0,6

antagonism

1,2 ± 0,4

antagonism

2,4 ± 0,6

antagonism

 

2:1

1,1 ± 0,3

antagonism

0,7 ± 0,2

synergy

1,4 ± 0,2

antagonism

Mtx

1:1

1,4 ± 0,4

antagonism

0,9 ± 0,4

synergy

0,9 ± 0,3

synergy

B

       

Dose Reduction index values (mean ± s.e.)

  

75%

90%

95%

Drug combination

Nutlin-3a

Chemotherapy

Nutlin-3a

Chemotherapy

Nutlin-3a

Chemotherapy

OSA

Nutlin-3a+Dox 1:1

1.5 ± 0.4

6.8 ± 3

1.4 ± 0.4

6.8 ± 2

1.3 ± 0.4

7.2 ± 2

 

Nutlin-3a+Dox 1:2

2.6 ± 0.5

2.5 ± 0.6

2.5 ± 0.5

3.2 ± 0.5

2.5 ± 0.6

3.8 ± 0.7

 

Nutlin-3a+Dox 2:1

1.9 ± 0.3

7.6 ± 2

1.4 ± 0.1

7.8 ± 2

1.2 ± 0.0

8 ± 2

 

Nutlin-3a+Cis 1:1

2.0 ± 0.5

2.0 ± 0.4

1.6 ± 0.4

1.9 ± 0.5

1.4 ± 0.4

1.9 ± 0.6

 

Nutlin-3a+Cis 1:2

2.6 ± 0.7

1.3 ± 0.3

2.1 ± 0.5

1.2 ± 0.3

1.8 ± 0.5

1.2 ± 0.3

 

Nutlin-3a+Cis 2:1

3.5 ± 2

6.3 ± 2

2.4 ± 1

4.7 ± 1

1.8 ± 0.8

4.1 ± 1

 

Nutlin-3a+Mtx 1:1

1.0 ± 0.1

3.7 ± 0.9

0.7 ± 0.2

4.7 ± 0.6

0.7 ± 0.3

5.7 ± 1

T778

Nutlin-3a+Dox 1:1

2.2 ± 0.5

8.1 ± 2

2.1 ± 0.6

14.1 ± 6

2.1 ± 0.7

21.1 ± 9

 

Nutlin-3a+Dox 1:2

1.7 ± 0.4

3.4 ± 1

1.2 ± 0.3

3.7 ± 1

1.0 ± 0.2

4.0 ± 1

 

Nutlin-3a+Dox 2:1

1.2 ± 0.2

9.2 ± 3

0.8 ± 0.2

9.3 ± 3

0.6 ± 0.2

9.5 ± 3

 

Nutlin-3a+Cis 1:1

2.1 ± 0.2

2.3 ± 0.4

1.8 ± 0.2

2.9 ± 0.9

1.6 ± 0.2

3.7 ± 2

 

Nutlin-3a+Cis 1:2

3.7 ± 1.2

2.0 ± 0.6

3.4 ± 1

2.9 ± 2

3.3 ± 1

4.1 ± 3

 

Nutlin-3a+Cis 2:1

3.2 ± 1

6.8 ± 2

2.8 ± 1

9.9 ± 6

2.5 ± 1

13.5 ± 9

 

Nutlin-3a+Mtx 1:1

5.2 ± 2

3.1 ± 1

3.9 ± 2

2.3 ± 0.9

3.5 ± 2

1.8 ± 0.8

U2OS

Nutlin-3a+Dox 1:1

1.2 ± 0.2

9.5 ± 4

1.1 ± 0.4

6.0 ± 2

1.2 ± 0.5

4.8 ± 2

 

Nutlin-3a+Dox 1:2

1.2 ± 0.4

4.2 ± 2

1.3 ± 0.4

4.2 ± 2

1.3 ± 0.4

4.2 ± 2

 

Nutlin-3a+Dox 2:1

1.1 ± 0.4

13.1 ± 5

1.1 ± 0.5

10.6 ± 4

1.2 ± 0.5

9.3 ± 3

 

Nutlin-3a+Cis 1:1

1.8 ± 0.5

3.0 ± 0.7

1.9 ± 1

2.6 ± 1

2.1 ± 1

2.8 ± 2

 

Nutlin-3a+Cis 1:2

1.6 ± 0.4

1.4 ± 0.4

1.4 ± 0.6

1.0 ± 0.3

1.4 ± 0.7

0.9 ± 0.4

 

Nutlin-3a+Cis 2:1

1.4 ± 0.2

6.1 ± 3

1.1 ± 0.2

4.1 ± 0.8

0.9 ± 0.2

3.5 ± 0.7

 

Nutlin-3a+Mtx 1:1

1.5 ± 0.4

6.9 ± 2

1.3 ± 0.4

6.2 ± 2

1.1 ± 0.4

5.8 ± 2

  1. A Combination Index (CI) values listed in the table are means ± standard error of the mean (SE) for Fa-values > 0.5, indicating additivity, more than additivity (synergy) or less than additivity (antagonism). Values were determined experimentally and calculated using the Chou and Talalay method and CalcuSyn software. Relative growth was assessed 120 h after drug treatment. Data is shown as combinations of Nutlin-3a with Doxorubicin, Cisplatin or Methotrexate in 1:1, 1:2 and 2:1 ratios. Since Nutlin-3a is not active in RMS13 and SaOS-2 it was by definition not possible to calculate their CI. B Dose Reduction Index (DRI) values for the three combinations at 75, 90 and 95% levels of growth inhibition of OSA, T778 and U2OS cell growth.
  2. CI < 1: more than additivity (synergy)
  3. CI = 1: additivity
  4. CI > 1: less than additivity (antagonism)
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BMC Cancer

ISSN: 1471-2407

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