. 2018 Aug;366(2):303–313. doi: 10.1124/jpet.118.249359

TABLE 4.

In vitro effects of nicotine in combination with chemotherapy on lung cancer

Lung Cancer Cell Line	Nicotine	Chemotherapy	Duration of Treatment	Serum Concentration	Cellular Response (Assay)	Result (Relative to Chemotherapy Alone)	Reference
A549	1 μM	Cisplatin 40 μM	24 h	10%	Apoptosis (annexin V)	30% decrease^†	Jin et al. (2004)
A549, H157	1 μM	Cisplatin 40 μM	6%–48 h	10%	Apoptosis (annexin V)	0%–40% decrease^†	Xin and Deng (2005)
A549, H157	1 μM	Cisplatin 40 μM	24 h	10%	Apoptosis (annexin V)	40% decrease^†	Xin and Deng (2005)
LKR	1 μM	Cisplatin 5 μM	Nicotine for 1 h, then cisplatin for 24 h	10%	Apoptosis (sub-G1)	20% decrease^†	Nishioka et al. (2010)
LKR	1 μM	Cisplatin 5 μM	Nicotine for 1 wk, then cisplatin for 24 h	10%	Apoptosis (sub-G1)	5% decrease^†	Nishioka et al. (2010)
H446	0.1–1 μM	Cisplatin 10 μM	12–72 h	10%	Viability (MTT)	13%–20% increase^†	Zeng et al. (2012)
			36 h		Apoptosis (AV/PI)	No effect (0.1–0.5 μM),
			36 h		Apoptosis (AV/PI)	15% decrease (1 μM)^*
H5800, LKR	0.5 μM	Cisplatin 0.6 μM	Nicotine for 24 h, then cotreatment of 48 h	10%	Apoptosis (annexin V)	60% decrease^*	Nishioka et al. (2014)
A549	1 μM	Cisplatin 20 μM	Nicotine for 24 h, then cisplatin for 24 h	10%	Apoptosis (AV/PI)	40% decrease^*	Liu et al. (2015)
A549	1 μM	Cisplatin 35 μM	Nicotine for 24 h, then cotreatment of 24 h	10%	Viability (MTT)	25% increase^*	Zhang et al. (2009)
		Etoposide 20 μM			Viability (MTT)	35% increase^*
		Cisplatin 35 μM			Apoptosis (DNA fragmentation ELISA)	35% decrease^*
		Etoposide 20 μM			Apoptosis (DNA fragmentation ELISA)	20% decrease^*
H1299	1 μM	Cisplatin 40 μM	96 h	10%	Apoptosis (annexin V)	40% decrease^*	Zhao et al. (2009)
H1299	1 μM	Etoposide 40 μM	96 h	10%	Apoptosis (annexin V)	30% decrease^*	Zhao et al. (2009)
A549	1 μM	Doxorubicin 10 μM	Nicotine for 1 h, then cotreatment of 48 h	10%	Viability (XTT)	25% increase^*	Nakada et al. (2012)
A549	1 μM	Doxorubicin 10 μM	Nicotine for 1 h, then cotreatment of 48 h	10%	Apoptosis (caspase-Glo 3/7)	300% decrease^*	Nakada et al. (2012)
PC9, HCC827	1 μM	Erlotinib 1 nM to 5 μM	72 h	10%	Viability (MTS)	IC₅₀ 31 nM → 43 nM (PC9),^* IC₅₀ 46 nM → 140 nM	Li et al. (2015)
201T	1 μM	Gefitinib 35 μM	48 h	10%	Viability (MTS)	30% increase	Carlisle et al. (2007)
PC9, 11–18	1 μM	Gefitinib 5 nM to 50 μM	72 h	10%	Viability (MTT)	IC₅₀ 24 nM → 22 nM, 0.35 μM → 0.33 μM	Togashi et al. (2015)
PC9, 11–18	1 μM	Gefitinib 5 nM to 50 μM	Nicotine for 3 mo, then cotreatment of 72 h	10%	Viability (MTT)	IC₅₀ 24 nM → 76 nM,^* 0.35 μM → 1.09 μM^*	Togashi et al. (2015)
A549, H460	1 μM	Paclitaxel 50 nM	Paclitaxel for 24 h, 24-h drug-free, nicotine for 24 h	10%	Proliferation (colony formation)	No effect	Kyte et al. (2018)
		Paclitaxel 50 nM	Nicotine for 24 h, then 24-h cotreatment		Proliferation (cell counting)	No effect
		Paclitaxel 100 nM	48 h		Apoptosis (AV/PI)	No effect
		Paclitaxel 100 nM	48 h		Apoptosis (sub-G1)	No effect

AV/PI, annexin V/propidium iodide; ELISA, enzyme-linked immunosorbent assay; MTS, (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium); MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; XTT, 2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt.

^{^†}

Statistical significance not indicated.

Statistically significant.