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Table 1 Cell cycle changes caused by metformin and/or nutlin-3a

From: Metformin produces growth inhibitory effects in combination with nutlin-3a on malignant mesothelioma through a cross-talk between mTOR and p53 pathways

Cells

Time (hrs)

Treatment

Cell cycle distribution (%)(Average ± SE)

Sub-G1

G1

S

G2/M

MSTO-211H

24

(-)

4.35 ± 0.22

56.30 ± 0.35

17.93 ± 0.04

20.88 ± 0.44

 

Met 20mM

5.43 ± 0.23

68.82 ± 0.25

12.91 ± 0.22

12.39 ± 0.23

 

Met 60 mM

10.92 ± 0.63

63.25 ± 1.75

4.71 ± 0.16

20.88 ± 2.13

 

Nut 10 μM

5.95 ± 0.11

84.18 ± 0.43

2.35 ± 0.16

7.32 ± 0.23

 

Met 20mM

+ Nut 10 μM

7.39 ± 0.14

72.91 ± 0.29

3.00 ± 0.14

16.23 ± 0.29

 

Met 60 mM

+ Nut 10 μM

10.56 ± 1.42

61.41 ± 1.50

7.93 ± 0.69

19.71 ± 0.71

48

(-)

0.76 ± 0.03

68.87 ± 0.65

12.70 ± 0.59

17.31 ± 0.20

 

Met 20mM

3.40 ± 0.06

70.64 ± 0.26

11.96 ± 0.06

13.43 ± 0.21

 

Met 60 mM

7.44 ± 0.12*

68.10 ± 0.30

5.29 ± 0.08

18.84 ± 0.13

 

Nut 10 μM

6.11 ± 0.22*

85.90 ± 0.25

1.89 ± 0.03

5.92 ± 0.13

 

Met 20mM

+ Nut 10 μM

6.51 ± 0.16

76.44 ± 0.24

2.82 ± 0.08

13.87 ± 0.18

 

Met 60 mM

+ Nut 10 μM

11.34 ± 0.22*

63.25 ± 0.24

2.97 ± 0.04

22.25 ± 0.22

72

(-)

1.15 ± 0.11

82.29 ± 0.39

4.04 ± 0.17

12.26 ± 0.18

 

Met 20mM

3.08 ± 0.09

76.19 ± 0.21

8.07 ± 0.14

12.25 ± 0.42

 

Met 60 mM

13.28 ± 0.27*

65.29 ± 1.07

4.99 ± 0.10

16.24 ± 0.71

 

Nut 10 μM

11.38 ± 0.14*

81.30 ± 0.28

1.88 ± 0.10

5.29 ± 0.13

 

Met 20mM

+ Nut 10 μM

7.39 ± 0.15

75.38 ± 0.21

2.63 ± 0.06

14.26 ± 0.23

 

Met 60 mM

+ Nut 10 μM

36.25 ± 0.44*

44.02 ± 0.25

3.28 ± 0.06

16.15 ± 0.26

NCI-H28

24

(-)

0.47 ± 0.04

60.27 ± 0.19

16.66 ± 0.34

22.06 ± 0.25

 

Met 20mM

0.43 ± 0.02

67.39 ± 0.41

11.76 ± 0.29

19.66 ± 0.13

 

Met 60 mM

0.89 ± 0.08

44.81 ± 0.07

15.01 ± 0.17

38.33 ± 0.17

 

Nut 10 μM

0.77 ± 0.02

40.63 ± 0.20

9.25 ± 0.42

47.61 ± 0.36

 

Nut 40 μM

1.22 ± 0.07

44.87 ± 0.57

15.17 ± 0.57

37.12 ± 0.65

 

Met 20mM

+ Nut 10 μM

1.25 ± 0.04

42.33 ± 0.36

13.30 ± 0.38

41.28 ± 0.06

 

Met 60 mM

+ Nut 40 μM

1.24 ± 0.15

48.20 ± 0.37

20.92 ± 0.17

28.35 ± 0.38

48

(-)

1.54 ± 0.05

60.08 ± 0.39

16.04 ± 0.36

21.88 ± 0.01

 

Met 20mM

0.45 ± 0.04

73.97 ± 0.18

6.35 ± 0.05

18.66 ± 0.10

 

Met 60 mM

1.06 ± 0.10

40.68 ± 0.08

14.65 ± 0.19

42.61 ± 0.19

 

Nut 10 μM

3.84 ± 0.10

43.82 ± 0.29

8.28 ± 0.20

42.47 ± 0.26

 

Nut 40 μM

2.50 ± 0.10

49.77 ± 0.22

10.35 ± 0.10

36.08 ± 0.21

 

Met 20mM

+ Nut 10 μM

0.91 ± 0.09

46.45 ± 0.74

9.23 ± 0.29

41.90 ± 0.90

 

Met 60 mM

+ Nut 40 μM

1.38 ± 0.12

49.24 ± 0.21

20.16 ± 0.30

27.63 ± 0.15

72

(-)

1.49 ± 0.02

64.68 ± 0.34

15.58 ± 0.03

17.79 ± 0.30

 

Met 20mM

0.52 ± 0.09

75.59 ± 0.14

4.52 ± 0.08

18.86 ± 0.21

 

Met 60 mM

1.50 ± 0.31

41.66 ± 0.37

15.31 ± 0.03

40.59 ± 0.27

 

Nut 10 μM

6.09 ± 0.20

43.98 ± 0.25

8.75 ± 0.23

39.57 ± 0.41

 

Nut 40 μM

8.96 ± 0.83

61.92 ± 0.79

7.31 ± 0.02

21.05 ± 0.49

 

Met 20mM

+ Nut 10 μM

1.01 ± 0.28

46.14 ± 0.66

9.14 ± 0.11

42.20 ± 0.41

 

Met 60 mM

+ Nut 40 μM

9.00 ± 0.72

44.61 ± 0.43

15.83 ± 0.25

29.48 ± 0.45

EHMES-10

24

(-)

0.46 ± 0.05

70.86 ± 0.69

9.64 ± 0.3

18.63 ± 0.57

 

Met 20mM

1.04 ± 0.06

73.58 ± 0.31

8.78 ± 0.05

16.18 ± 0.32

 

Met 60 mM

1.61 ± 0.06

67.93 ± 0.31

6.95 ± 0.14

23.13 ± 0.28

 

Nut 20 μM

1.19 ± 0.10

73.47 ± 0.21

10.38 ± 0.26

14.38 ± 0.29

 

Nut 60 μM

1.19 ± 0.08

80.17 ± 0.16

3.49 ± 0.06

14.74 ± 0.05

 

Met 20mM

+ Nut 20 μM

0.85 ± 0.02

76.79 ± 0.23

7.35 ± 0.09

14.61 ± 0.19

 

Met 60 mM

+ Nut 60 μM

2.37 ± 0.19

73.06 ± 0.38

5.2 ± 0.38

18.93 ± 0.32

48

(-)

0.92 ± 0.04

73.14 ± 0.06

10.34 ± 0.23

15.22 ± 0.35

 

Met 20mM

1.46 ± 0.13

61.87 ± 0.16

13.00 ± 0.12

23.04 ± 0.21

 

Met 60 mM

2.67 ± 0.12*

66.72 ± 0.12

9.32 ± 0.11

20.73 ± 0.13

 

Nut 20 μM

1.62 ± 0.20

67.78 ± 0.21

12.12 ± 0.17

18.02 ± 0.17

 

Nut 60 μM

1.85 ± 0.16*

84.44 ± 0.12

3.32 ± 0.05

10.15 ± 0.06

 

Met 20mM

+ Nut 20 μM

1.35 ± 0.04

66.71 ± 0.35

13.01 ± 0.32

18.19 ± 0.42

 

Met 60 mM

+ Nut 60 μM

4.57 ± 0.17*

74.63 ± 0.17

5.44 ± 0.16

15.11 ± 0.2

72

(-)

2.18 ± 0.55

56.86 ± 0.62

12.2 ± 0.75

27.79 ± 1.57

 

Met 20mM

1.89 ± 0.11

63.77 ± 0.19

11.90 ± 0.21

21.64 ± 0.42

 

Met 60 mM

3.07 ± 0.14*

64.22 ± 0.13

8.22 ± 0.12

23.99 ± 0.22

 

Nut 20 μM

0.73 ± 0.03

67.46 ± 0.28

11.05 ± 0.19

20.22 ± 0.39

 

Nut 60 μM

3.47 ± 0.11*

84.27 ± 0.25

3.4 ± 0.17

8.74 ± 0.07

 

Met 20mM

+ Nut 20 μM

1.27 ± 0.03

70.85 ± 0.23

9.44 ± 0.43

17.85 ± 0.19

 

Met 60 mM

+ Nut 60 μM

13.85 ± 0.86*

62.12 ± 0.26

6.35 ± 0.25

17.57 ± 0.86

  1. *P < 0.05, compared between combination and either metformin or nutlin-3a single treatment. N = 3
  2. Met Metformin, Nut Nutlin-3a