Table 1.

The impact of LDN and low doses of MNTX on cancer cells in in vitro and in vivo models.

LDN/Low-Dose MNTX Concentration/Dose	Cancer	Results	References
LDN 0.5, 1.5, 2, 3 and 5 mg/mL	In vitro model of Hela and Siha, cervical cancer cells	LDN inhibits the proliferation of cervical cancer cells in a time- and dose-dependent manner. After 48 h of LDN treatment, the IC50 was 1.26 mg/mL. After treatment with LDN for 48 h, the inhibition rates of different concentrations (0.5 mg/mL, 1.5 mg/mL, 2 mg/mL, 3 mg/mL, 5 mg/mL) were 17.27 ± 5%, 47.44 ± 3%, 68.59 ± 4%, 84.68 ± 1%, and 95.47 ± 1%, respectively.	[73]
LDN 1 nM LDN 10 nM	In vitro model of human colorectal cancer cell lines HCT116 and human lung cancer cell lines A549	Cell counting experiments revealed that the reduction in cell number was associated with a fall in cell viability, which suggests an active cytotoxic response was achieved. Flow cytometric analysis of the cell cycle showed significant increases in the sub-G1 peak following an LDN-then-recovery schedule with concomitant emptying of cells from G1 and G2.	[72]
Low-dose MNTX 0.10–100 nM	In vitro model of human non-small cell lung cancer cells lines NSCLC	Treatment with MNTX inhibited cell invasion and anchorage-independent growth by 50–80%.	[10]
LDN intraperitoneal (IP) injection 0.1 mg/kg	SCC-1 oral squamous cell carcinoma xenografts in Foxn1nu (nude) mice	LDN increased the latency from visible to measurable tumors up to 1.6-fold. OGF, low-dose naltrexone, and imiquimod treatment markedly reduced tumor volume and weight and decreased DNA synthesis in tumors.	[76]
LDN 0.1 mg/kg	SKOV-3 human ovarian cancer xenografts in athymic nu/nu female mice	LDN-treated mice displayed a visible reduction in tumor burden relative to the control group. Compared to the total number of nodules detected in the control group, animals treated with LDN displayed a 39% reduction.	[45]
LDN 0.5 mg/kg, LDN 5 mg/kg LDN 10 mg/kg	Hela and Siha human cervical cancer xenografts in BALB/C nude mice	LDN significantly decreased the expression of PI3K, PDK1, and mTOR. There was no difference in the expression of VEGF and AKT, but the expression of pVEGFR2 and pAKT was downregulated. The expression of pVEGFR, PI3K, PDK1, pAKT, and mTOR significantly reduced after LDN treatment, especially in the 10 mg/kg group. Compared to the control group, the 10 mg/kg LDN treatment group showed significant differences in tumor growth inhibition from day 22 of the treatment, while the 5 mg/kg LDN-treated group showed such differences from day 31. The time of significant difference in mice treated with 0.5 mg/kg LDN was 34 days	[74]
LDN 0.5 mg/kg, LDN 5 mg/kg, LDN 10 mg/kg	Human cervical cancer cell lines Hela and Siha, xeno-grafts in BALB/C nude mice	The ratio of M2 macrophage membrane markers labeled with CD206+ showed a decrease in the LDN group compared with the control group. The proportion of TAMs significantly reduced after LDN treatment, especially in the 10 mg/kg group. LDN suppressed the M2 macrophages and reduced the expression of IL-10.	[73]