TABLE 6

In vivo effects of nicotine on lung cancer

Lung Cancer Model	Mouse Strain	Nicotine Dose, Route of Administration	Duration of Treatment	Tumor Measurement	Result (Relative to Control)	Reference
N592	Nude	20 or 200 μg/d, s.c. (osmotic minipump)	14 days	Volume	No effect	Pratesi et al. (1996)
N417 (nicotine-treated, 500 μM for 7 days)	Nude	—	—	Volume	100% increase^*	Martínez-García et al. (2010)
N417 (nicotine-treated, 500 μM for 7 days)	Nude	—	—	Growth (Ki-67⁺)	30% increase	Martínez-García et al. (2010)
DMS-53	Nude	24 mg/kg per day, s.c. (osmotic minipump)	1 mo	Volume	250% increase^*	Improgo et al. (2013)
DMS-53	Nude	24 mg/kg per day, s.c. (osmotic minipump)	1 mo	Weight	380% increase^*	Improgo et al. (2013)
A549	Nude, ovariectomized	200 μg/ml in drinking water	38 days	Volume	20% increase	Jarzynka et al. (2006)
				Growth (Ki-67⁺)	300% increase^*
				Microvascular density	80% increase
H460	Foxn1^nu	60 μg, s.c., every other day	6 or 28 days	Volume	No effect	Warren et al. (2012)
				Angiogenesis (HIF-1α)	75% increase (acute),
				Angiogenesis (HIF-1α)	1300% increase (chronic)^*
A549	SCID-Beige	i.p., every other day (dose not indicated)	7 wk	Size (luminescence)	120% increase^*	Pillai et al. (2015)
A549	SCID-Beige	i.p., every other day (dose not indicated)	7 wk	Lung metastasis	75% increase^†	Pillai et al. (2015)
A549	Nude BALB/c	1 μM in drinking water	20 days	Volume	88% increase^†	Liu et al. (2015)
A549	Nude BALB/c	1 μM in drinking water	20 days	Weight	185% increase^*	Liu et al. (2015)
A549 (nicotine-treated, 5 μM)	Nude BALB/c	—	—	Angiogenesis (hemoglobin)	170% increase^*	Shi et al. (2015)
PC9	BALB/cAJc1-nu/nu	0.6 mg/kg, i.v., 5×/wk or 100 μg/ml in drinking water, then combination with erlotinib (100 mg/kg, p.o.)	Nicotine for 18 days	Volume	24% and 39% increase for i.v. and p.o., respectively^*	Li et al. (2015)
PC9	BALB/cAJc1-nu/nu		Nicotine + Erlotinib for 10 days	Volume	200% and 300% increase for i.v. Nic + ER and p.o. Nic + ER, respectively, compared with ER alone^*	Li et al. (2015)
Line1	BALB/c	1 mg/kg, i.p., 3×/wk	2 wk	Volume	225% increase^*	Davis et al. (2009)
				Tumor recurrence	200% increase^*
				Lung metastasis	700% increase^*
		25 mg/kg per day via transdermal patch		Volume	65% increase^*
		25 mg/kg per day via transdermal patch		Lung metastasis	230% increase^*
LLC	C57BL/6J	100 μg/ml in drinking water	16 days	Volume	100% increase^*	Heeschen et al. (2001)
LLC	C57BL/6	100 μg/ml in drinking water	14 days	Volume	75% increase^*	Nakada et al. (2012)
LLC	C57BL/6J	24 mg/kg per day, s.c. (osmotic minipump)	7 days	Volume	No effect	Kyte et al. (2018)
NNK, i.p.	A/J	1 mg/kg, i.p., 3×/wk	4 wk	Area	135% increase^†	Davis et al. (2009)
NNK, i.p.	A/J	1 mg/kg, i.p., 3×/wk	4 wk	Lung metastasis	60% increase^*	Davis et al. (2009)
NNK, i.p.	Ab6F1 (A/J × C57BL/6J)	100 μg/ml in drinking water	12 wk	Multiplicity	No effect	Maier et al. (2011)
				Volume	No effect
				Incidence	35% increase
				Growth (Ki-67⁺)	No effect
NNK, i.p.	A/J	200 μg/ml in drinking water	2, 44, or 46 wk	Volume	No effect	Murphy et al. (2011)
				Multiplicity	No effect
				Incidence	No effect
NNK, i.p.	A/J	1 mg/kg, i.p.,	10 wk	Incidence	125% increase^*	Iskandar et al. (2013)
NNK, i.p.	A/J	3× per week	10 wk	Volume	80% increase^*	Iskandar et al. (2013)
Spontaneous tumor	Kras^LA2/+ C57BL/6J	100 μg/ml in drinking water	6 wk	Multiplicity	No effect	Maier et al. (2011)
Spontaneous tumor	Kras^LA2/+ C57BL/6J	100 μg/ml in drinking water	6 wk	Growth (Ki-67⁺)	No effect	Maier et al. (2011)

HIF-1α, hypoxia-inducible factor 1-α; i.p., intraperitoneal; LLC, Lewis lung carcinoma; NNK, nicotine-derived nitrosamine ketone; p.o., oral.
↵* Statistically significant.
↵^† Statistical significance not indicated.