Vita Min C Combined With Parthenolide Inhibits HepG-2 Cell Migration And Invasion By Reg Ulating TGF-β/smad Signaling Pathway

Objective: Primary liver cancer is one of the most diagnosed cancer types in the world and the third leading cause of cancer-related deaths.The characteristics of liver cancer include high recurrence rate,easy metastasis and increased incidence.The main cause of death in patients with primary liver cancer is invasion and metastasis,and its invasion and migration are a complex and m ulti-factor regulation process.Epithelial-mesenchymal transition(EMT)plays a vital role in the process of tumor metastasis.For the treatment of liver cancer,it is still necessary to consider continuous adjuvant therapy even after surgery to suppress the recurrence and metastasis of liver cancer.However,many chemotherapy treatments have large side effects and some have developed drug resistance.Therefore,continuous exploration of adjuvant cancer treatment The combination of Chinese medicine and Chinese medicine has shown great potential.Vitamin C(VC)is a low-toxicity,low-cost drug.VC treatment of cancer is a hot topic.When used in combination with chemotherapy drugs and anti-inflammatory drugs,the anti-cancer effect of vitamin C has also been significantly improved.As adjuvant therapy or adjuvant drug therapy,VC has good performance.The combination of VC and various chemotherapy drugs can slow down the growth of xenograft tumors and reduce the general toxicity of chemotherapy drugs.Through parenteral administration,vitamin C can reach the anti-cancer pharmacological level.VC is not only almost non-toxic to patients,but also has a wide range of curative effects in the treatment of cancer.But in fact,it is very difficult to increase the blood concentration of vitamin C,and oral administration can hardly meet the requirements.Therefore,it is of great significance to reduce the anti-cancer pharmacological concentration of VC through drug combination.Sesquiterpene lactones are herbal components with biological activity and structural diversity,including parthenolide(PTL),which has been used as an anti-inflammatory drug.PTL is an important natural metabolite in asteraceae medicinal plants,and has good anti-inflammatory and anti-cancer effects.VC and PTL have been proved to have anticancer activity in various mechanisms and cancers.PTL not only has the ability to inhibit the migration of tumor cells,but also has a lot of overlap with the anticancer mechanism of vitamin C.they may have a good synergistic effect.Therefore,our study aims to explore the effect of VC combined with PTL on the migration and invasion of hepatoma cells and its possible mechanism.Therefore,our study aims to explore the effect of VC combined with PTL on the migration and invasion of liver cancer cells and the possible mechanism of action.Research methods: The aim of this study was to investigate the effect of VC combined with PTL at the concentration of 0.2 mmol /L on the viability of Hep G-2cells;Cell scratch experiment was used to observe the effect of VC(0.2 mmol /L)combined with PTL(5 μmol /L,10 μmol /L)on the migration ability of Hep G-2 cells;Transwell assays was used to detect the effect of VC(0.2 mmol /L)combined with PTL(5 μmol /L,10 μmol /L)treatment on the invasion ability of Hep G-2 cells;To detect the effect of VC combined with PTL on the protein expression level of Hep G-2cell migration and invasion related proteins(E-cadherin,N-cadherin,MMP-9,TGF-β,Smad2,p-Smad2,Smad3,p-Smad3)by Western blot.Results:VC at 0.2 mmol /L alone had no significant effect on the survival rate of Hep G-2 cells.When combined with PTL,the survival rate of Hep G-2 cells decreased with the increase of PTL concentration.Compared with the control group,VC combined with 20 μmol /L and 40 μmol /L PTL significantly inhibited the proliferation of Hep G-2 cells and showed obvious cytotoxicity;VC can inhibit the migration and invasion ability of Hep G-2 to a certain extent,and can significantly reduce the migration and invasion ability of cells when combined with PTL,and it was found by Western blot that VC alone had a reduced effect on MMP9 and N-cadherin.But it is not obvious.After VC combined with PTL treatment,E-cadherin was significantly up-regulated,and the expression of MMP9 and N-cadherin protein was significantly reduced;at the same time,VC alone and combined with PTL treatment both down-regulated TGF-β,p-Smad2,and p-Smad3 The role of expression level.Conclusion:VC alone has no significant effect on the survival rate of Hep G-2 cells at the concentration of 0.2 mmol /L,and the proliferation of Hep G-2 cells is inhibited with the increase of PTL concentration when VC is combined with PTL;VC combined with PTL can interfere with the epithelial mesenchymal transition(EMT)process of Hep G-2 by inhibiting TGF-β/ smad signaling pathway,and inhibit its migration and invasion ability.The combination of VC and PTL may become a potential adjuvant therapy for clinical treatment of liver cancer.