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. 2015 Nov 18;6(37):39398–39407. doi: 10.18632/oncotarget.6347

Table 1. Effects of antidiabetic biguanides on spontaneous and induced carcinogenesis in rodents.

Target organ Species, strain Sex Carcinogenic agent1 Drug2 Dose Route3 Effect4 References
Mammary gland C3H/Sn mice F MMTV PF 2 mg/mouse oral ↓ [18, 19]
FVB/N mice F HER-2/neu MF 100 mg/kg d.w. ↓ [37,45]
FVB/N mice F HER-2/neu MF 250 mg/kg i.p. ↓ [46]
FVB/N mice F MMTV-neu;p53+/− MF 1500 mg/kg diet = [47]
FVB/N-Tg mice F MMTV-PyVT PF 1.65 mg/ml d.w. ↓ [48]
FVB/N-Tg mice F MMTV-PyVT MF 2 mg/ml d.w. ↓ [48]
SHR mice F Spontaneous MF 100 mg/kg d.w. = [49]
LIO rats F Spontaneous PF 2 mg/rat oral ↓ [21, 36]
LIO rats F DMBA PF 5 mg/rat oral ↓ [17, 22]
LIO rats F DMBA BF 5 mg/rat oral ↓ [24]
LIO rats F NMU PF 1 mg/rat oral ↓ [23]
SD rats F NMU MF 5 mg/kg
50 mg/kg		 oral
oral		 =
↓		 [50]
SD rats F NMU MF 110-220 mg/kg diet ↓ [51]
SD rats F NMU MF 5-50 mg/kg diet = [47]
SD rats F NMU MF 9.3 mmol/kg diet = [52]
SD rats F NMU PF 5 mmol/kg diet = [52]
SD rats F NMU BF 7.6 mmol/kg diet ↓ [52]
Wistar rats F NMU+OV X MF 2 mg/mL d.w. [53]
LIO rats F X-rays PF 5 mg/rat oral ↓ [30]
Pituitary gland LIO rats F Spontaneous BF 5 mg/rat oral ↓ [20]
LIO rats F X-rays PF 5 mg/rat oral ↓ [30]
Thyroid gland LIO rats F Spontaneous BF 5 mg/rat oral ↓ [20]
LIO rats F Spontaneous PF 2 mg/rat oral ↓ [21]
Skin SHR mice F BP MF 200 mg/L d.w. ↓ [54]
SHR mice F BP MF 200 mg/L d.w. ↓ [55]
FVB/N mice F DMBA+TPA MF 2-250 mg/kg d.w. ↓ [56]
Soft tissues Outbred mice M MCA PF 5 mg/kg oral ↓ [29]
SHR mice F BP MF 200 mg/L d.w. ↓ [57]
Uterus Balb/c mice F E2, tamoxifen MF 50 mg/kg diet ↓ [58]
129/Sv mice F Spontaneous MF 600 mg/L d.w. ↓ [59]
F344 rats F Spontaneous PF 400-800 ppm diet ↓ [60]
LIO rats F Spontaneous PF 2 mg/rat oral ↓ [21, 36]
LIO rats F X-rays PF 5 mg/rat oral ↓ [30, 36]
Cervix utery SHR mice F BP MF 200 mg/L d.w. ↓ [61]
Lung
 A/J mice M&F NNK MF 250 mg/kg i.p. ↓ [62]
LID mice M&F NNK MF 250 mg/kg d.w. ↓ [63]
129/Sv mice M Urethan MF 200 mg/L d.w. ↓ [64]
Swiss H mice M&F Tobacco smoking MF 800 pm diet ↓ [65]
Oral mucosa C57BL/6 mice F 4-NQO MF 50 mg/kg i.p. ↓ [66]
Pancreas Hamsters M NBOPA MF 320 mg/kg oral ↓ [35]
p48Cre/+. LSL-ras G12D mice M&F Spontaneous MF 1000-2000 ppm diet ↓ [67]
KPC mice M&F Spontaneous MF 1 mg/ml d.w. ↓ [68]
LSA+L-Kras; trp53 mice M&F Adenovirus MF 125 mg/kg i.p. ↓ [69]
Pancreatic islets CD1 mice M HCFD MF 50-250 mg/kg diet ↓ [70]
Liver
 C57BL/6 mice M NDEA MF 250 mg/kg diet ↓ [71]
C57BL/6 mice M Spontaneous MF 10 mg/kg diet ↓ [72]
C57BL/6 (HBxTg) mice M HBx transgenic MF 250 vg/kg oral = [73]
C57BL/6 mice M High fat diet MF 250 mg/kg d.w. ↓ [74]
db/db mice F NDEA MF 300 mg/kg d.w. ↓ [75]
Wistar rats M NDEA MF 125 mg/kg oral ↓ [76]
Wistar rats M NDEA MF 250 mg/kg oral ↓ [77]
Small intestines ApcMin/+ mice M&F Spontaneous MF 250 mg/kg diet ↓ [78]
PTEN+/− mice M&F Spontaneous MF 300 mg/kg d.w. = [79]
PTEN+/− mice M&F Spontaneous PF 300 mg/kg d.w. = [79]
Colon BALB/c mice M&F AOM MF 250 mg/kg diet ↓ [80]
BALB/c mice M&F AOM MF 250 mg/kg d.w. ↓ [81]
BALB/c mice M&F AOM MF 250 mg/kg i.p. ↓ [81]
Swiss mice M DMH MF 100-200 mg/kg diet ↓ [82]
IСR mice M DMH + DSS MF 240 mg/kg diet ↓ [83]
LIO rats F DMH PF 5 mg/rat oral ↓ [25, 26]
F344 rats M AOM MF 15 mg/kg d.w. ↓ [80]
F344 rats M&F AOM MF 500-1000 ppm diet = [84]
F344 rats M&F AOM MF 1000 ppm diet = [85]
F344 rats M&F AOM MF 1000 ppm diet = [86]
SD rats M DMH+STZ MF 150 mg/kg oral ↓ [87]
Wistar M DMH MF 100-300 mg/kg oral ↓ [88]
Kidney Swiss H mice M&F Tobacco smoking MF 800 ppm diet ↓ [65]
LIO rats M&F NEU, t.pl. BF 5 mg/rat oral ↓ [28]
Lymphoid tissue B6C3F1 mice M&F Spontaneous PF 300-625 mg/kg diet ↓ [60]
PTEN+/− mice M&F Spontaneous MF 300 mg/kg d.w. = [79]
PTEN+/− mice M&F Spontaneous PF 300 mg/kg d.w. ↓ [79]
C57BL/6-Ly5.2 MF γ-irradiation MF 250 mg/kg oral ↓ [89]
LIO rats F X-rays PF 5 mg/rat oral ↓ [30]
Nervous suystem LIO rats M&F NMU, tr.pl. BF 5 mg/rat oral ↓ [27]
LIO rats M&F NEU, tr.pl. BF 5 mg/rat oral ↓ [28]
Total tumors B6C3F1mice M&F Spontaneous PF 400-800 ppm diet = [60]
SHR mice F Spontaneous MF 600 mg/L d.w. = [49]
129/Sv mice M&F Spontaneous MF 600 mg/L d.w. ↓ [59]
129/Sv mice M Spontaneous MF 100 mg/kg s.c. ↓ [90]
129/Sv mice F Spontaneous MF 100 mg/kg s.c. = [90]
B6C3F1 mice M Spontaneous MF 10 mg/kg diet = [76]
C57BL/6 mice M Spontaneous MF 10 mg/kg diet = [76]
LIO rats F Spontaneous BF 5 mg/rat oral ↓ [20]
LIO rats F Spontaneous PF 2 mg/rat oral ↓ [21]
LIO rats F X-rays PF 5 mg/rat oral ↓ [30, 36]
F344 rats M&F Spontaneous PF 400-800 ppm diet = [60]

Notes: M, Male; F, Female.

1

Carcinogenic agents: AOM, azoxymethane; BP, benzo(a)pyrene; DMBA, 7,12-dimethylbenz(a)anthracene; DMH, 1,2-dimethylhydrazine; DSS, dextrane sodium sulphur; E2, estradiol-17β; HCHFD, high carbohydrate fat diet; HER-2/neu, transgen; LID, liver-IGF-1-deficient mice; MCA, 20-methylcholanthrene; MMTV, murine mamary tumor virus; NBOPA, N-nitrosobis(2-oxopropyl)amine; NDEA, N-nitrosodiethylamin; NEU, N-nitrosoethylurea; NMU, N-nitrosomethylurea; NKK, 4–(methylnitroosamino)–1–(3-pyridyl)-1-butanone; 4-NQO, 4–nitroquinoline-1-oxide; STZ, streptozotocin; TPA,12-O-tetradecanoylphorbol-13-acetate.

2

Drugs: BF. buformin; MF, metformin; PF, phenformin.

3

Route of administration: diet, with lab chow; d.w., drinking water; i.p., intraperitoneally; oral, gavage; s.c., subcutaeously; tr.pl., transplacental.

4

Effect: ↓, inhibition of tumor incidence and/or tumor multiplicity, and/or increase of tumor latency; =, no effect.