In this study, neural stem cells (NSCs)-derived
enzyme/
prodrug therapy (NDEPT) was used to treat primary
lung cancer or metastatic
lung cancer in the brain. To confirm the anti-
tumor effect of NSCs expressing carboxyl
esterase (CE), A549
lung cancer cells were treated with HB1.F3.CE cells and
CPT-11. A significant decrease in the viability/proliferation of
lung cancer cells was observed compared to negative controls or cells treated with
CPT-11 alone. To produce a mouse model of primary
lung cancer or
lung cancer metastasis to the brain, A549 cells were implanted in the dorsal area of the mouse or right hemisphere.
CM-DiI pre-stained stem cells were implanted near the primary
lung cancer tumor mass or in the contralateral brain. Two days after stem cells injection, mice were inoculated with
CPT-11 (13.5 kg/mouse/day) via
intraperitoneal injection. In the primary
lung cancer mouse models,
tumor mass was 80% lower in response to HB1.F3.CE in conjunction with
CPT-11, while it was only reduced by 40% in the group treated with
CPT-11 alone. Additionally, therapeutic efficacy of co-treatment with stem cells and
CPT-11 was confirmed by detection of apoptosis and
necrosis in primary and metastatic
lung cancer tissues. By secreting
VEGF,
tumor cells modulate Erk1/2 and Akt signaling and migration of stem cells. This further increased
tumor-selectivity of stem cell/
prodrug co-
therapy. Overall, these results indicate that NSCs expressing the therapeutic gene may be a powerful tool for treatment of primary
lung cancer or
metastasis of
lung cancer to the brain.