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The retinoic acids (RA), physiologic derivatives of the Vitamin A (Retinol), are signaling molecules involved in cell growth, differentiation and carcinogenesis and may antagonize cancer progression. In a previous work, we demonstrated that the murine lung tumor LP07 cells are able to express the RA Receptors (RAR a and b) and the binding protein CRBP-1, involved in retinol-mediated signaling. Besides, we demonstrated that ATRA inhibited in vitro LP07 growth and diminished the secretion of the proteolytic enzyme uPA, involved in tumor invasion.

The aim of this work was to evaluate the effect of Retinol on LP07 growth, in comparison with ATRA, and to study the effect of ATRA on in vitro invasive capacity and in vivo tumor growth and dissemination.

Retinol (1uM) inhibited the in vitro growth of LP07 cells after 4 days treatment (p<0.05), suggesting that cells are able to metabolize the Retinol to ATRA. LP07 cells were more sensitive to the inhibitory growth effect of Retinol than ATRA, at the same dose. On the other hand the treatment during 5 days with ATRA 1uM diminished 49% the invasion in matrigel, employing transwell chambers (p<0.05).

Besides, LP07 cells were s.c inoculated in syngeneic Balb/c mice (n=20) and when tumors were palpable, oral treatment with ATRA (2 mg/animal, twice a week) was administered for 15 days. ATRA induced a significant decrease in tumor growth. At 30 days post-inoculation the tumor size from treated animals was 2.47± 1.5 cm3 vs 3.67±1.5 cm3 observed in control ones (p<0.05). Mice treated with ATRA showed also a significantly lower number of spontaneous metastasis. On the other hand, mice i.v inoculated with LP07 cells pre-treated during 5 days with ATRA 1uM showed a marked decrease in the number and size of experimental lung nodules (p<0.05). In conclusion, ATRA is able to modulate mechanisms involved in tumor progression, such as growth, invasion and metastatic dissemination. Our results also suggest that Vitamin A could be growth inhibitory in this model of murine lung cancer.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA