Studies Of The Effective Component Of Licorice Affecting The Subcellular Localization Of Thioredoxin

With the rapid progress of our society, people’s living standards are improved steadily.However, a series of pollution problems brought about by current developments and the bad habits developed by people in the long-term life, are likely to lead to the internal disorder of body’s normal cell cycle, and thus, make the cell physiological function and other aspects seriously disordered, eventually deteriorated and evolved into a "cancer".Thioredoxin(Thioredoxin-1, Trx) are a class of small molecules and widely distributed multifunctional proteins, which are more conserved in evolution, belonging to the class of redox protein family. At present, studies about a variety of tumor cell lines indicate that Trx expression levels positively correlated with tumor cell drug-resistance; meanwhile, clinical exploration also confirmed that cancer patients with higher level of Trx expression are more easily to be significant drug-resistance for a variety of chemotherapeutic agents. This is mainly due to the chemotherapy drugs can stimulate Trx to move into the nucleus and keep reduction activity, and then by increasing the activity of the related nuclear transcription factor to make tumor cells have the ability to resist apoptosis and eventually be resistant then. Therefore, Trx has very important significance as a potential target for anti-cancer therapy.Chinese medicine has a long history in our country. Because the rich source of medicines and lower drug side-effects,it is very popular in patients. Therefore, the task of exploring effective anti-cancer medicine is imminent.This article mainly use the natural licorice mixed component and its main mono-active ingredient into human HeLa cells, then study its role in Trx subcellular localization with the help of relevant technology.Firstly, use compound liquorice tablets(whose main ingredient is licorice extract) as an experimental drug and set different drug concentrations treatment groups with the same reaction time and different time treatment groups with the same drug concentration. Western blot results indicate that, Trx expression levels in nuclear and cytoplasm of above two treatment groups, both show a reduction trend as drug concentration becomes higher and treatment time lasts. Then it can be concluded that there existed related content in licorice mixed component, which can influence Trx subcellular localization.Then, use two main active mono-therapy ingredients glycyrrhizin(saponins) and glycyrrhizin(flavonoids) respectively as an experimental drug, setting different drug concentrations treatment groups with the same reaction time and different time treatment groups with the same drug concentration. Western blot results show that, Trx expression levels in nuclear and cytoplasm of above two treatment groups, both show a reduction trend as drug concentration becomes higher and treatment time lasts. Therefore, it demonstrated that those two active mono-therapy ingredients play an important role in the fall of Trx subcellular localization, and they shall be the effective components of licorice. At the same time, as two contrast drugs, notoginsenoside R1(saponins) and rue leaves glycosides(flavonoids) are used to treat HeLa cells in the same method as the above experimental settings. Western blot results found that both of them did not make the expression of Trx in its nucleus and cytoplasm appear significantly decline. Thus it illustrated that glycyrrhizin and glycyrrhizin are specific drugs for he expression of Trx in its nucleus and cytoplasm.Finally, respectively combine glycyrrhizin and glycyrrhizin with anticancer drugs cisplatin, paclitaxel and epirubicin, setting a series of combined experimental groups of two drugs. Western blot and tetrazolium salt(MTT) assay results indicated that the cytotoxicity of licorice is small, and when the concentration of the chemotherapy drug remained in the low-dose, localization expression of Trx in its nucleus and cytoplasm all showed a gradual decline trend as the licorice acid/liquiritin drug concentration increased. At the same time, combinations of low-dose anticancer drugs with the two single drug showed similar results with simple high-dose chemotherapy drugs in the change of Trx subcellular localization. So glycyrrhizin and glycyrrhizin in combination with clinic chemotherapeutic drugs are expected to reduce the dose of the chemotherapeutic drugs, which shows a potential clinical significance in reducing the side effects of chemotherapy on patients and improving cancer treatment effect.