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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (1): 67-75.doi: 10.3736/jcim20120111

• Original Experimental Research • Previous Articles     Next Articles

Effects of platycodin D in combination with different active ingredients of Chinese herbs on proliferation and invasion of 4T1 and MDA-MB-231 breast cancer cell lines

Han Xiang-hui1,2,Ye Yi-yi1,Guo Bao-feng1,Liu Sheng1()   

  1. 1. Institute of Traditional Chinese Medicine Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    2. School of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2011-08-18 Accepted:2011-09-09 Online:2012-01-20 Published:2018-09-21
  • Contact: Liu Sheng E-mail:yige823@yahoo.com.cn

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OBJECTIVE: To investigate the effects of platycodin D in combination with different active ingredients of Chinese herbs under different therapeutic principles on proliferation and invasion of 4T1 and MDA-MB-231 breast cancer cell lines.METHODS: The effective doses of platycodin D, Ophiopogon total saponins, curcumenol and osthole in inhibiting proliferation of breast cancer cell lines 4T1 and MDA-MB-231 were detected by methyl thiazolyl tetrazolium (MTT) assay, respectively. Optimized combinations of platycodin D with Ophiopogon total saponins, curcumenol, or osthole were determined by uniform design method. Effects of the optimized combinations of platycodin D with the three ingredients on proliferation and invasion of 4T1 and MDA-MB-231 cells were verified and evaluated by MTT assay and Transwell chamber test, respectively.RESULTS: Verifying study showed that the inhibitory effects of platycodin D in combination with curcumenol or osthole on proliferation of 4T1 and MDA-MB-231 cells were better than those of platycodin D in combination withOphiopogon total saponins and each ingredient used alone (P<0.05 or P<0.01). The inhibitory effect of platycodin D in combination with Ophiopogon total saponins or osthole on invasion of 4T1 cells was significantly better than those of platycodin D in combination with curcumenol and each ingredient used alone (P<0.05 or P<0.01). Moreover, the inhibitory effect of platycodin D in combination with curcumenol or osthole on invasion of MDA-MB-231 cells was significantly better than that of platycodin D in combination with Ophiopogon total saponins (P<0.01).CONCLUSION: The optimized combinations of platycodin D with three different active ingredients of Chinese herbs under different therapeutic principles can significantly inhibit the proliferation and decrease the invasion of 4T1 and MDA-MB-231 cells. Different platycodin D combinations have different potency in suppressing breast cancer cell proliferation and invasion.

Key words: platycodin D, drugs, Chinese herbal, compatibility, breast neoplasms, cell proliferation, neoplasm invasiveness, uniform design

Table 1

Schedule of uniform design of platycodin D in combination with Ophiopogon total saponins"

Number Platycodin D (μg/mL) Ophiopogon total
saponins (μg/mL)
1 8.6 5.0
2 6.0 7.2
3 18.0 6.0
4 5.0 12.5
5 7.2 18.0
6 12.5 20.0
7 20.0 15.0
8 15.0 8.6
9 10.5 10.5

Table 2

Schedule of uniform design of platycodin D in combination with curcumenol"

Number Platycodin D (μg/mL) Curcumenol (μg/mL)
1 8.6 5.0
2 6.0 7.2
3 18.0 6.0
4 5.0 12.5
5 7.2 18.0
6 12.5 20.0
7 20.0 15.0
8 15.0 8.6
9 10.5 10.5

Table 3

Schedule of uniform design of platycodin D in combination with osthole"

Number Platycodin D (μg/mL) Osthole (μg/mL)
1 8.6 5.0
2 6.0 7.2
3 18.0 6.0
4 5.0 12.5
5 7.2 18.0
6 12.5 20.0
7 20.0 15.0
8 15.0 8.6
9 10.5 10.5

Table 4

Effects of platycodin D, Ophiopogon total saponins, curcumenol and osthole on proliferation of breast cancer cell lines 4T1 and MDA-MB-231 ($\bar{x}$±s)"

Group n Dosage (μg/mL) OD value
4T1 cell line MDA-MB-231 cell line
Control 5 0.860±0.012 0.660±0.022
Platycodin D 5 5 0.760±0.021** 0.540±0.035**
5 10 0.600±0.033** 0.470±0.049**
5 20 0.410±0.008** 0.370±0.035**
5 40 0.230±0.023** 0.160±0.005**
5 80 0.110±0.004** 0.050±0.004**
Ophiopogon total saponins 5 5 0.800±0.032* 0.640±0.003*
5 10 0.840±0.020 0.590±0.012**
5 20 0.680±0.050** 0.460±0.014**
5 40 0.370±0.012** 0.230±0.002**
5 80 0.110±0.004** 0.093±0.001**
Curcumenol 5 5 0.890±0.031 0.480±0.085*
5 10 0.800±0.039* 0.530±0.011*
5 20 0.690±0.081* 0.480±0.053*
5 40 0.270±0.009** 0.310±0.045**
5 80 0.060±0.007** 0.140±0.025**
Osthole 5 5 0.760±0.032** 0.520±0.008**
5 10 0.640±0.070** 0.440±0.009**
5 20 0.420±0.037** 0.220±0.009**
5 40 0.230±0.071** 0.090±0.004**
5 80 0.120±0.036** 0.072±0.003**

Table 5

Effects of the uniform design-based combinations of platycodin D with Ophiopogon total saponins on proliferation of breast cancer cell lines 4T1 and MDA-MB-231 ($\bar{x}$±s)"

Number OD value
4T1 cell line MDA-MB-231 cell line
1 0.510±0.190 0.120±0.068
2 0.700±0.120 0.190±0.011**
3 0.460±0.058** 0.180±0.005**
4 0.700±0.084 0.220±0.006
5 0.580±0.100 0.190±0.003
6 0.400±0.058** 0.170±0.020*
7 0.410±0.072** 0.200±0.055
8 0.640±0.014 0.150±0.009*
9 0.690±0.048 0.096±0.006**
Control 0.780±0.073 0.230±0.024

Table 6

Effects of the uniform design-based combinations of platycodin D with curcumenol on proliferation of breast cancer cell lines 4T1 and MDA-MB-231 ($\bar{x}$±s)"

Number OD value
4T1 cell line MDA-MB-231 cell line
1 0.420±0.061** 0.070±0.012
2 0.700±0.075 0.120±0.019*
3 0.370±0.045** 0.110±0.011**
4 0.660±0.046* 0.180±0.016
5 0.360±0.079** 0.210±0.021
6 0.240±0.018** 0.170±0.033
7 0.220±0.037** 0.200±0.017
8 0.380±0.028** 0.130±0.012**
9 0.650±0.042* 0.053±0.045**
Control 0.780±0.073 0.230±0.024

Table 7

Effects of the uniform design-based combinations of platycodin D with osthole on proliferation of breast cancer cell lines 4T1 and MDA-MB-231 ($\bar{x}$±s)"

Number OD value
4T1 cell line MDA-MB-231 cell line
1 0.700±0.150 0.150±0.018**
2 0.580±0.030 0.170±0.010**
3 0.480±0.092 0.092±0.009
4 0.560±0.006* 0.072±0.140**
5 0.280±0.030** 0.061±0.100**
6 0.110±0.003** 0.070±0.140**
7 0.130±0.002** 0.065±0.140**
8 0.400±0.046** 0.110±0.230**
9 0.520±0.016* 0.079±0.200**
Control 0.780±0.073 0.230±0.024

Table 8

Results of regression analysis of the uniform design"

Group 4T1 cell line MDA-MB-231 cell line
Regression equation Optimized
combination
(μg/mL)		 Regression equation Optimized
combination
(μg/mL)
Platycodin D
plus Ophiopogon
total saponins		 Y=0.127+0.022 7X1+0.090 8X2–
0.001 54X1×X1–0.003 97X2×X2		 15+20 Y=0.403–0.040 8X1–0.008 04X2+
0.001 63X1×X1+0.000 435X2×X2		 12+9
Platycodin D
plus curcumenol		 Y=0.310–0.008 39X1+0.081 5X2–
0.000 610X1×X1–0.003 89X2×X2		 15+20 Y=0.269–0.035 7X1–0.000 279X2+
0.001 46X1×X1+0.000 330X2×X2		 12+5
Platycodin D
plus osthole		 Y=0.893–0.011 8X1–0.017 5X2–
0.000 321X1×X1–0.000 581X2×X2		 15+20 Y=0.271–0.004 90X1–0.019 6X2+
0.000 109X1×X1+0.000 572 2X2×X2		 20+17

Table 9

Inhibitory effects of the optimized combinations of platycodin D with three other ingredients on proliferation of breast cancer cell lines 4T1 and MDA-MB-231 ($\bar{x}$±s)"

Group n 4T1 cell line MDA-MB-231 cell line
Dosage
(μg/mL)		 Cell inhibition rate (%) Dosage
(μg/mL)		 Cell inhibition rate (%)
Control 5 / 0 / 0
Platycodin D 5 25 68.1±3.8** 25 50.1±4.1**
Curcumenol 5 25 57.2±5.6** 25 39.0±8.3*
Ophiopogon total saponins 5 25 47.8±3.5** 25 41.3±2.9*
Osthole 5 25 67.6±1.6** 25 85.4±1.3**
Platycodin D plus curcumenol 5 15+20 78.9±3.9**△△▲▲☆☆ 12+5 74.2±2.8**△△▲▲☆☆
Platycodin D plus Ophiopogon total saponins 5 15+20 54.6±2.3** 12+9 52.0±2.1**■
Platycodin D plus osthole 5 15+20 92.2±2.7**△△□□☆☆ 20+17 79.5±3.5**△△☆☆

Table 10

Effects of the best combinations of platycodin D with three other ingredients on invasion of breast cancer cell lines 4T1 and MDA-MB-231 ($\bar{x}$±s)"

Group n 4T1 cell line MDA-MB-231 cell line
Dosage
(μg/mL)		 Number of invasion cell Dosage
(μg/mL)		 Number of invasion cell
Control 3 / 174.6±62.8 / 388.8±193.4
Platycodin D 3 25 93.2±42.8* 25 28.6±34.6**
Curcumenol 3 25 329.4±117.7 25 26.2±18.3**
Ophiopogon total saponins 3 25 59.8±27.2** 25 395.2±126.3
Osthole 3 25 79.0±38.4** 25 31.8±16.4**
Platycodin D plus curcumenol 3 15+20 109.4±79.1* 12+5 36.6±20.4**☆☆
Platycodin D plus Ophiopogon total saponins 3 15+20 19.6±7.9**△■★★ 12+9 120.4±73.3**■■
Platycodin D plus osthole 3 15+20 32.6±20.4**△□★★ 20+17 33.0±7.9**☆☆

Figure 1

Effects of the optimized combinations of platycodin D with three other ingredients on invasion of breast cancer cell line 4T1 (Light microscopy, × 200) A: Control group; B: Platycodin D group; C: Curcumenol group; D: Ophiopogon total saponins group; E: Osthole group; F: Platycodin D plus curcumenol group; G: Platycodin D plus Ophiopogon total saponins group; H: Platycodin D plus osthole group."

Figure 2

Effects of the optimized combinations of platycodin D with three other ingredients on invasion of breast cancer cell line MDA-MB-231 (Light microscopy, ×200) A: Control group; B: Platycodin D group; C: Curcumenol group; D: Ophiopogon total saponins group; E: Osthole group; F: Platycodin D plus curcumenol group; G: Platycodin D plus Ophiopogon total saponins group; H: Platycodin D plus osthole group."

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