TABLE 4

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

Lung Cancer Cell LineNicotineChemotherapyDuration of TreatmentSerum ConcentrationCellular Response (Assay)Result (Relative to Chemotherapy Alone)Reference
A5491 μMCisplatin 40 μM24 h10%Apoptosis (annexin V)30% decreaseJin et al. (2004)
A549, H1571 μMCisplatin 40 μM6%–48 h10%Apoptosis (annexin V)0%–40% decreaseXin and Deng (2005)
24 h40% decrease
LKR1 μMCisplatin 5 μMNicotine for 1 h, then cisplatin for 24 h10%Apoptosis (sub-G1)20% decreaseNishioka et al. (2010)
Nicotine for 1 wk, then cisplatin for 24 h5% decrease
H4460.1–1 μMCisplatin 10 μM12–72 h10%Viability (MTT)13%–20% increaseZeng et al. (2012)
36 hApoptosis (AV/PI)No effect (0.1–0.5 μM),
15% decrease (1 μM)*
H5800, LKR0.5 μMCisplatin 0.6 μMNicotine for 24 h, then cotreatment of 48 h10%Apoptosis (annexin V)60% decrease*Nishioka et al. (2014)
A5491 μMCisplatin 20 μMNicotine for 24 h, then cisplatin for 24 h10%Apoptosis (AV/PI)40% decrease*Liu et al. (2015)
A5491 μMCisplatin 35 μMNicotine for 24 h, then cotreatment of 24 h10%Viability (MTT)25% increase*Zhang et al. (2009)
Etoposide 20 μM35% increase*
Cisplatin 35 μMApoptosis (DNA fragmentation ELISA)35% decrease*
Etoposide 20 μM20% decrease*
H12991 μMCisplatin 40 μM96 h10%Apoptosis (annexin V)40% decrease*Zhao et al. (2009)
Etoposide 40 μM30% decrease*
A5491 μMDoxorubicin 10 μMNicotine for 1 h, then cotreatment of 48 h10%Viability (XTT)25% increase*Nakada et al. (2012)
Apoptosis (caspase-Glo 3/7)300% decrease*
PC9, HCC8271 μMErlotinib 1 nM to 5 μM72 h10%Viability (MTS)IC50 31 nM → 43 nM (PC9),* IC50 46 nM → 140 nMLi et al. (2015)
201T1 μMGefitinib 35 μM48 h10%Viability (MTS)30% increaseCarlisle et al. (2007)
PC9, 11–181 μMGefitinib 5 nM to 50 μM72 h10%Viability (MTT)IC50 24 nM → 22 nM, 0.35 μM → 0.33 μMTogashi et al. (2015)
Nicotine for 3 mo, then cotreatment of 72 hIC50 24 nM → 76 nM,* 0.35 μM → 1.09 μM*
A549, H4601 μMPaclitaxel 50 nMPaclitaxel for 24 h, 24-h drug-free, nicotine for 24 h10%Proliferation (colony formation)No effectKyte et al. (2018)
Paclitaxel 50 nMNicotine for 24 h, then 24-h cotreatmentProliferation (cell counting)No effect
Paclitaxel 100 nM48 hApoptosis (AV/PI)No effect
Paclitaxel 100 nM48 hApoptosis (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.