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. 2019 Jun 17;19:589. doi: 10.1186/s12885-019-5791-1

Table 1.

Characteristics of prospective studies on BBR

Author, year, country Species, strain, gender, age Model cell line Experiment Control Outcome
Dosage Frequency Adnimistration Duration type mean0 Sd0 n0 mean1 Sd1 n1 p value
Breast cancer
 Elisa Pierpaoli, 2015, Italy [10] mice, FVB/N, F, 4w SK-BR-3 2.5 mg/kg biw ip 32.5w DMSO VD 16.81 7.24 10 12.09 1.98 10 0.07
 Yuwan Zhao, 2017, China [11] mice, BALB/c, F, 6w MDA-MB-231 100 mg/kg tiw po 3w DMSO TV 2.70 0.18 7 0.68 0.08 7 < 0.01
BW 24.40 0.69 7 22.48 0.81 7 < 0.01
 Alaa Refaat, 2013, Japan [12] mice, BALB/c, F, 6w 4 T1 100 mg/kg qd po 4.3w CMC TW 0.21 0.01 6 0.15 0.01 6 < 0.01
 Sangmin Kim, 2018, Korea [13] mice, Balb/c, F, 6-8w MDA-MB-231 0.1% BBR in the drinking water Daily free intake po 6.6w – TV 0.42 0.18 5 0.21 0.08 5 0.05
 Kalyani Chowdary Karnam, 2017, India [14] rats, SD, F, 6.4–8.3w Induced by DMBA 50 mg/kg [pretreatment] tiw po 4w Corn oil TV 3.79 0.90 6 0.63 0.30 6 < 0.01
TW 9.64 0.90 6 3.80 0.99 6 < 0.01
50 mg/kg [posttreatment] TV 3.79 0.90 6 1.31 0.60 6 < 0.01
TW 9.64 0.90 6 5.71 1.32 6 < 0.01
 Elisa Damiani, 2015, Italy [15] miceFVB/NF4w HER2/neu transgenic mice 2.5 mg/kg biw ip NR Sterile saline VD 16.77 5.31 7 11.07 1.75 9 0.03
 Ke Su, 2016, China [16] mice, Balb/c, F, 6w MDA-MB-231 10 mg/kg q4d ip 3w DMSO TV 0.59 0.27 6 0.27 0.12 6 0.02
TW 0.50 0.11 6 0.29 0.06 6 < 0.01
BW 22.59 7.31 6 19.10 3.71 6 0.32
Liver cancer
 Guan-Yu Wang, 2009, China [17] mice, Balb/c, M, 6w HEPG2 40 mg/kg qd ip 1.4w Saline TV 3.31 0.38 5 2.21 0.22 6 < 0.01
BW 3.13 0.43 5 4.62 0.41 6 < 0.01
80 mg/kg TV 3.31 0.38 5 1.43 0.13 5 < 0.01
BW 3.13 0.43 5 3.74 0.36 5 0.04
 Jing Li, 2015, Canada [18] mice, Balb/c, NR, 6-8w H22 50 mg/kg qd po 2w Water TV 4.24 0.56 10 0.33 0.35 10 < 0.01
 Chi Man Tsang, 2015, China [19] mice, NR, NR, NR MHCC-97 L-luciferase 10 mg/kg qod ip 5w Saline TV 1.00 0.05 7 0.21 0.03 7 < 0.01
VD 12.58 2.94 7 2.18 1.29 7 < 0.01
Colon cancer
 Norio Iizuka, 2002, Japan [20] mice, Balb/c, M, 6w Colon26/clone 20 0.1% BBR in the driNRing water Daily free intake po 2w – TW 0.22 0.15 9 0.25 0.12 9 0.65
BW 18.20 1.50 9 18.40 1.80 9 0.80
0.2% BBR in the driNRing water TW 0.22 0.15 9 0.25 0.15 9 0.68
BW 18.20 1.50 9 22.20 1.50 9 < 0.01
0.4% BBR in the driNRing water TW 0.22 0.15 9 0.24 0.18 9 0.80
BW 18.20 1.50 9 20.90 4.20 9 0.10
 H Ruan, 2017, China [21] mice, Balb/c, NR, 6-7w KM12C/shCtrl 10 mg/kg qd ip 2w DMSO TV 1.26 0.97 6 0.79 0.53 6 0.32
KM12C/shRXRα 1.54 0.92 6 1.40 0.46 6 0.76
 Yuchen Cai, 2013, Japan [22] mice, Balb/c, NR, 5w HT-29 10 mg/kg qd po 2w Sterile water TV 6.11 3.01 10 4.33 2.42 10 0.16
BW 6.60 3.60 10 4.90 3.20 10 0.28
30 mg/kg TV 6.11 3.01 10 4.09 1.76 10 0.08
BW 6.60 3.60 10 3.90 2.70 10 0.07
50 mg/kg TV 6.11 3.01 10 3.34 1.31 11 0.01
BW 6.60 3.60 10 3.60 2.50 11 0.04
nasopharyngeal carcinoma
 Chao Wang, 2017, China [23] mice, NOD/SCID, F, 8w HONE-1 10 mg/kg tiw ip 3w DMSO TV 0.58 0.06 5 0.10 0.03 5 < 0.01
TW 0.15 0.01 5 0.02 0.01 5 < 0.01
 Chi Man Tsang, 2013, China [24] mice, NR, M, 6-8w C666–1 5 mg/kg qod ip 6w DMSO TV 0.15 0.05 5 0.04 0.03 5 < 0.01
10 mg/kg 0.15 0.05 5 0.02 0.02 4 < 0.01
Lung cancer
 Michael A. James, 2011, Missouri [25] mice, Balb/c, M, 4-6w A549 1800 ppm Daily free intake po 4w DMSO TV 0.06 0.02 3 0.02 0.02 4 0.05
5400 ppm 0.06 0.02 3 0.01 0.01 2 0.04
 Santosh K. Katiyar, 2009, Alabama [26] mice, Balb/c, F, 6-7w A549 50 mg/kg qd po 7w PBS TV 1.40 0.07 10 0.99 0.04 10 < 0.01
TW 2.32 0.27 10 2.02 0.30 10 0.03
100 mg/kg TV 1.40 0.07 10 0.60 0.03 10 < 0.01
TW 2.32 0.27 10 1.16 0.21 10 < 0.01
200 mg/kg TV 1.40 0.07 10 0.30 0.06 10 < 0.01
TW 2.32 0.27 10 0.62 0.09 10 < 0.01
H1299 50 mg/kg TV 1.59 0.10 10 1.36 0.05 10 < 0.01
TW 2.71 0.31 10 2.36 0.29 10 0.02
100 mg/kg TV 1.59 0.10 10 1.05 0.05 10 < 0.01
TW 2.71 0.31 10 1.82 0.29 10 < 0.01
200 mg/kg TV 1.59 0.10 10 0.61 0.02 10 < 0.01
TW 2.71 0.31 10 1.15 0.10 10 < 0.01
Gastric cancer
 Junxiong Wang, 2016, China [27] mice, Balb/c, F, 5w BGC823 50 mg/kg qd po 4w NR TV 2.28 0.24 3 0.73 0.13 3 < 0.01
TW 1.37 0.37 3 0.32 0.08 3 < 0.01
BW 2.51 0.69 3 0.10 0.46 3 < 0.01
 Hongli Li, 2016, China [28] mice, Balb/c, M, 4w MGC803 15 mg/kg qd po 3.3w NR TV 0.85 0.29 6 0.44 0.09 6 0.02
TW 0.68 0.18 6 0.42 0.07 6 < 0.01
Neuroepithelial tumor
 Juan Wang, 2015, China [29] miceBalb/cNN – 100 mg/kg qd po 3w NR TV 0.04 0.02 8 0.02 0.00 8 0.05
 Yuxue Sun, 2018, China [30] miceBalb/cN6-8w C6 10 mg/kg qd ip 1w DMSO TV 0.77 0.22 7 0.35 0.06 7 < 0.01
Endometrial carcinoma
 Yu Wang, 2018, China [31] mice, Balb/c, NR, 6w HEC-1-A 50 mg/kg qd po 4w DMSO TV 1.01 0.13 6 0.65 0.06 6 < 0.01
100 mg/kg 1.01 0.13 6 0.34 0.04 6 < 0.01
Esophageal cancer
 Kewei Ren, 2016, China [32] mice, Balb/c, M, 6-8w Eca9706 20 mg/kg qd po 7w DMSO TV 6.37 0.25 5 5.05 0.60 5 < 0.01
TW 2.66 0.29 5 1.82 0.21 5 < 0.01
Tongue squamous cell carcinima
 Yung-Tsuan Ho, 2009, China [33] mice, Balb/c, F, 6w SCC-4 10 mg/kg q4d ip 4w DMSO TV 0.18 0.06 6 0.03 0.02 6 < 0.01
TW 0.26 0.16 6 0.12 0.09 6 0.11
Cholangiocarcinoma
 Nattapong Puthdee, 2013, Japan [34] hamster, Syrian, M, 4-5w Ham-1 10 mg/kg qd po 3w sterile water TW 0.70 0.18 5 0.67 0.11 5 0.79
Sarcoma
 Lei Zhang, 2012, China [35] mice, Kunming, NR, 6w S180 30 mg/kg qd ip NR NR TW 2.20 0.93 10 1.26 0.54 9 0.02
BW 2.71 2.20 10 −2.54 3.24 9 < 0.01

Mean0: mean value in control group (cm3 for tumor volume, g for tumor weight and body weight, mm/mm2 for vessel density); Sd0: standard difference in control group; N0: sample size in control group; Mean1: mean in berberine group; Sd1: standard difference in berberine group; N1: sample size in berberine group; M: male; F: femle; NR: non reported; TV: tumor volume; TW: tumor weight; VD: vessel density; BW: body weight