ABSTRACT
Uterine leiomyoma （UL）， the most common benign tumor of the reproductive system in women of childbearing age， is characterized by clinical symptoms such as increased menstrual flow， prolonged menstrual period， breast tenderness，backache， lower abdominal pain and mass in the lower abdomen. With the continuous progress of modern society， the age of women's marriage and childbirth is gradually pushed back， which to a certain extent has led to an increase in the probability of modern women suffering from UL. Relevant literature shows that the incidence of UL is about 70%， and 25%-50% of the patients have clinical symptoms， seriously endangering women's physical health. The prevention and treatment of UL by modern medicine is currently limited to two aspects： drug control of estrogen and progesterone levels and surgical removal. Traditional Chinese medicine（TCM）has shown obvious advantages in improving the clinical symptoms of UL patients， with very broad application prospects as it can regulate body's Qi and blood on the basis of syndrome differentiation， treatment and overall concepts. Lichongtang， as a famous TCM prescription for replenishing Qi， activating blood and removing blood stasis， was created by ZHANG Xi-chun， a famous Chinese medicine doctor in the Qing dynasty， and recorded in the Records of Tradition Chinese and Western Medicine in Combination. It is widely used in the field of gynecological diseases in clinical practice. Studies have shown that Lichongtang is effective in treating UL. Clinical observations show that Lichongtang can significantly relieve the clinical symptoms of UL patients such as prolonged menstrual period， dysmenorrhea， waist and abdomen swelling and irregular vaginal bleeding， with the characteristics of stable curative effect， high safety， less side effect and low recurrence rate. The experimental results show that Lichongtang has a comprehensive regulatory effect on UL through inhibiting the proliferation of UL cells and inducing apoptosis， reducing serum estrogen and progesterone level， regulating the apoptosis pathway of tumor cells， and promoting the degradation of extracellular matrix（ECM）. After retrieval in PubMed， CNKI and other databases， the authors made a review by summarizing the theories， clinical efficacy and action mechanisms of Lichongtang in the treatment of UL， in order to provide reference for the follow-up in-depth study of pharmacological mechanism of Lichongtang and its further clinical application and promotion.
ABSTRACT
Objective: To investigate the effect of modified Lichongtang combined with 5-fluorouracil (5-FU) on epithelial-mesenchymal transition (EMT) of human hepatoma HepG2 cells. Method: The growth of HepG2 cells was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and the effect of Chinese medicine and 5-FU alone or combined use on the growth of HepG2 cells was analyzed by the principle of efficacy. The growth curves of HepG2 cells were plotted to determine the relationship between drug effect and combination index as well as the interaction between drugs. Scratch test was used to detect the effect of modified Lichongtang combined with 5-FU on the migration of HepG2 cells. Cell invasion assay (transwell chamber) was used to detect the effect of modified Lichongtang combined with 5-FU on the invasion ability of HepG2 cells. Real-time quantitative polymerase chain reaction (PCR) was used to detect the effect of modified Lichongtang combined with 5-FU on EMT-related genes E-cadherin, N-cadherin and Zinc finger transcription factors (snail, twist) mRNA expression after 24 hours of treatment on HepG2 cells. The expression levels of E-cadherin, N-cadherin, Snail and Vimentin in HepG2 cells were detected by Western blot after treatment by modified Lichongtang combined with 5-FU for 24 hours. Result: MTT assay showed that with the increase of drug concentration, the inhibitory effect of modified Lichongtang, 5-FU alone or combined use on HepG2 cell growth was also increased. Statistical analysis showed that the combined use of these two drugs at a low dosage could produce better synergistic effect on HepG2 cells after 24 hours of treatment. Therefore, modified Lichongtang and 5-FU were selected to treat HepG2 cells for 24 hours. 25%inhibitory concentration (IC25) was 800 mg·L-1 modified Lichongtang, 3.125 mg·L-15-FU. Blank group, 5-FU group, Lichongtang+5-FU group, and modified Lichongtang group were set for follow-up experiments. Scratch and invasion experiments showed that modified Lichongtang, 5-FU alone and combined use can inhibit HepG2 cell migration and invasion ability (PPPPPPPPPPConclusion: Modified Lichongtang combined with 5-FU can produce a better synergistic effect on HepG2 cells at a low dosage for 24 hours, and can significantly inhibit the migration and invasion of hepatocellular carcinoma cells, up-regulate the expression of E-cadherin, down-regulate the expression of N-cadherin, Snail, Vimentin and Twist in hepatocellular carcinoma cells. Inhibition of tumor cell proliferation, migration, invasion and EMT-related gene expression may be associated with enhancing the efficacy of chemotherapy drugs, and may act as one of the mechanisms for synergistic effect of modified Lichongtang combined with 5-FU.
ABSTRACT
Objective: To investigate the effect of modified Lichongtang combined with 5-fluorouracil (5-FU) on tumor epithelial-mesenchymal transition (EMT) in H22 tumor-bearing mice. Method: Mouse models of transplanted hepatoma were constructed. After tumor formation, they were randomly divided into 4 groups:blank group, 5-FU group(2.5 mg·kg-1 5-FU intraperitoneal injection), modified Lichongtang combined with 5-FU group (5-FU+Chinese medicine group), and modified Lichongtang group (Chinese medicine group,25 g·kg-1 gavage),n=10 in each group. The effect of modified Lichongtang combined with 5-FU on the tumor inhibition rate of subcutaneous transplanted tumor was observed. The gene expression levels of E-cadherin,N-cadherin,Snail,and Twist in transplanted tumor were observed by Real-time PCR. The protein expression levels of E-cadherin,N-cadherin,Snail,and Vimentin were detected by using Western blot. Result: The tumor inhibiting rate was 59.18%,84.42%,and 10.39% respectively in 5-FU group, 5-FU+Chinese medicine group,and Chinese medicine group. All of these can inhibit the growth of liver cancer transplantation tumor, and the tumor inhibiting rate of 5-FU+Chinese medicine group was significantly higher than that in 5-FU group (PPPPPPPPPPPConclusion: Modified Lichongtang, 5-FU and their combination have inhibitory effect on the growth of transplanted tumors of hepatocarcinoma mice, and the combination of the two drugs can enhance the effect of chemotherapy and to some extent inhibit the toxicity of 5-FU. The mechanism may be related to the inhibition of liver cancer EMT.