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Table 1 Characteristics of prospective studies on BBR

From: Anticancer effect of berberine based on experimental animal models of various cancers: a systematic review and meta-analysis

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
  1. 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
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