Study On The Inhibitory Effect Of Novel Curcumin Nanoparticles On Proliferation Of Lewis Lung Carcinoma In Vitro And In Vivo

BackgroundThe morbidity and mortality of lung cancer is the highest in malignant tumors, and the morbidity of lung cancer apprars a increasing trend. Drug resistance and side effects caused the chemotherapy effect is not ideal. In recent years, curcumin(Cur) extracted from traditional chinese medicine turmeric has become a hotspot, some researches confirm Cur can inhibit the proliferation of lung cancer, breast cancer, liver cancer, and has fewer side effects, low-cost advantages. However, poor water solubility and instability limit its clinical application of Cur. Pharmaceutical preparations using nanotechnology to produce nanoparticles can improve its water solubility and stability. In this study, a new type of curcumin nanoparticles(Cur-NPs) on the proliferation of Lewis lung carcinoma will be investgateed in vitro and in vivo.ObjectiveTo determine the effect of Cur-NPs on the proliferation of lewis lung carcinoma in vitro and in vivo and investgate mechanism of Cur induce Lewis lung carcinoma apoptosis.Methods1. Lewis lung carcinoma cells were cultured with different concentrations of Cur-NPs and Cur, and the cell proliferation was evaluated by MTT assay.2. Cell apoptosis, cell cycle arrest, reactive oxygen accumulation, intracellular Ga2+ accumulation and mitochondrial membrane potential were evaluated by flow cytometry.3. C57BL/6J mice model of Lewis lung carcinoma was established, to investigate the tumor inhibitory effect of Cur-NPs on Lewis lung carcinoma.4. Akt, Fox O1 and Bim protein expression in Lewis lung cancer were dected by western blot. Result1. Both Cur-NPs and Cur can inhibited Lewis lung carcinoma cells proliferation. IC50 of Cur-NPs and Cur were10.65 mol/L and 34.91 mol/L respectively.2. The ratio of Cur and Cur-NPs inhibited Lewis cell cycle in S phase were(81.57±9.15) % and(92.20± 7.65) % respectively. The ratio of Cur and Cur-NPs induced apoptosis of Lewis lung cancer cells were(7.43 ±1.13) % and(67.69± 9.86) % respectively. Reactive oxygen concentration of Cur and Cur-NPs were(2088.01± 238.19) and(2568.67 ±361.85) respectively. Intracellular Ca2+ accumulation of Cur and Cur-NPs were(52.11 ± 11.28) and(97.85 ± 15.68) respectively. Mitochondrial membrane potential of Cur and Cur-NPs were(128.97 ± 18.56) and(94.00 ± 12.11) respectively.Both Cur-NPs and Cur can arrest cell cycle in S phase, induce apoptosis, elevate intracellular calcium concentration, increase the intracellular concentration of active oxygen, reduce the mitochondrial membrane potential,and Cur-NPs has stronger effect than Cur(P<0.05).3. After 14 days of treatment, mice were sacrificed and dissected tumor, Ct group, Cur group, Cur-NPs and NPs group, tumor weight were(4.10 ± 0.31)g,(2.50± 0.27) g,(1.40± 0.19) g and(4.04 ± 0.32) g respectively. The inhibition rates of Cur group and Cur-NPs group were(39.02 ± 7.63) % and(65.85± 10.81) % respectively.Both Cur-NPs and Cur can inhibit the growth of Lewis lung carcinoma, Cur-NPs has stronger effect than Cur(P<0.05).4. Cur inhibited Akt protein expression and promoted the protein expression of Fox O1 and Bim in vitro and in vivo(P<0.05).Conclusion1. Cur-NPs can enhance the inhibitory effects of Cur on Lewis lung carcinoma proliferation in vitro and in vivo.Both Cur-NPs and Cur induced apoptosis, arrested cell cycle at S phase, increase reactive oxygen accumulation and intracellular Ca2+ accumulation and decreased mitochondrial membrane potential.Cur-NPs has stonger effect than Cur.2. Cur induced apoptosis of Lewis lung cancer may through the PI3K/Akt-Fox O1-Bim signal pathway.