Molecular Mechanisms Of Vitamin C Against Pulmonary Metastasis

Lung cancer is currently a huge threat to human health and it is divided into primary lung cancer and pulmonary metastasis by source of pathogenesis.Vitamin C(Vc),as a dietary antioxidant,shows good anti-tumor activity in a variety of cancers,but there are few studies in pulmonary metastasis.This thesis mainly illustrated the anti-cancer activity of Vc against pulmonary metastasis and explored its molecular mechanisms.First,MTT assay,clone formation assay and wounding healing assay were performed to demonstrate that Vc could inhibit the proliferation and migration of lung cancer cells in a concentration-dependent manner and had little cytotoxic effect on normal lung cells.Second,Vc promoted oxidant stress in p53 null cells,and inhibited oxidant stress in p53wild-type cells.The results showed that the presence or increased level of p53 was closely related to antioxidant effects of Vc.Vc activated Nrf2/HO-1 pathway and further induced DNA damage and endogenous apoptosis through increasing γ-H2 A.X and cleaved caspases3 and 9 in both lung cancer cells.At last,to further validate the anti-cancer activity of Vc,a Kunming mouse pulmonary metastasis of H22 model was established.As a result,both intraperitoneal injection and oral administration of Vc could effectively inhibit the development of pulmonary metastasis through activating the expression of Nrf2/HO-1 and increasing expression of cleaved caspases 3 and 9.In conclusion,oral Vc or intraperitoneal injection of Vc could effectively inhibit pulmonary metastasis in H22 inbred pulmonary metastatic mice.It activated Nrf2/HO-1pathway and further induced DNA damage and endogenous apoptosis through increasingγ-H2 A.X and cleaved caspases 3 and 9 in both lung cancer cells.More importantly,these findings provide new clues for Vc treating pulmonary metastasis in clinic.