Characteristics and Research Progress of Traditional Chinese Medicine in Treatment of HER-2-Positive Breast Cancer： A Review / 中国实验方剂学杂志

Human epidermal growth factor receptor-2 （HER-2）-positive breast cancer has higher predilection to metastasize and invade other organs， leading to poor prognosis. The anti-HER-2 drugs， such as trastuzumab， pertuzumab， and trastuzumab emtansinehas， can remarkably prolong the disease free survival （DFS） of patients. However， frequent multidrug resistance， tumor recurrence and metastasis， and adverse reactions such as cardiotoxicity and gastrointestinal discomfort caused by adjuvant therapy are still challenges for the treatment of HER-2-positive breast cancer. The understanding of breast cancer in traditional Chinese medicine （TCM） has a long history. In thousands of years of inheritance and innovation， a standardized treatment system with TCM characteristics has been gradually formed， which shows unique advantages and significant curative effects in breast cancer treatment. The treatment principles of ''treatment based on syndrome differentiation''， ''treatment based on stages and types''， ''treatment according to individual conditions''， and ''treatment of different viscera and viscera based on the toxin and pathogen'' are closely related to the precise treatment concept. In view of the challenges in the treatment of HER-2-positive breast cancer， such as multidrug resistance， tumor recurrence and metastasis， cardiotoxicity， and gastrointestinal discomfort， this paper summarizes the characteristics of TCM in reversing the multidrug resistance， inhibiting tumor recurrence and metastasis， prolonging DFS， improving prognosis， reducing adverse reactions caused by adjuvant therapy， and improving the quality of life after breast cancer surgery according to the principles of reinforcing healthy Qi and eliminating pathogen， and treatment based on syndrome differentiation. This article is expected to serve as a reference for TCM treatment of HER-2 positive breast cancer.

COE inhibits vasculogenic mimicry in hepatocellular carcinoma via suppressing Notch1 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Vasculogenic mimicry (VM) has been suggested to be present in various malignant tumors and associated with tumor nutrition supply and metastasis, leading to poor prognosis of patients. Notch1 has been demonstrated to contribute to VM formation in hepathocellular carcinoma (HCC). Celastrus orbiculatus extract (COE), a mixture of 11 terpenoids isolated from the Chinese Herb Celastrus orbiculatus Vine, has been suggested to be effective in cancer treatment. AIM OF THE STUDY: In the current study, experiments were carried out to examine the effect of COE on VM formation and HCC tumor growth both in vitro and in vivo. MATERIALS AND METHODS: CCK-8 assay and Nikon live-work station were used to observe the viability of malignant cells treated with COE. Cell invasion was examined using Transwell. Matrigel was used to establish a 3-D culture condition for VM formation. Changes of mRNA and protein expression were examined by RT-PCR and Western Blot respectively. Tumor growth in vivo was monitored using in vivo fluorescence imaging device. PAS-CD34 dual staining and electron microscopy were used to observe VM formation. Immunohistochemical staining (IHC) was used to examine Notch1 and Hes1 expression in tumor tissues. RESULTS: Results showed that COE can inhibit HCC cells proliferation and invasion in a concentration-dependent manner. VM formation induced by TGF-ß1 was blocked by COE. In mouse xenograft model, COE inhibited tumor growth and VM formation. Both in vitro and in vivo studies showed that COE can downregulate expression of Notch1 and Hes1. CONCLUSION: The current results indicate that COE can inhibit VM formation and HCC tumor growth by downregulating Notch1 signaling. This study demonstrates that COE is superior to other anti-angiogenesis agents and can be considered as a promising candidate in HCC treatment.

Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling.

Hypervascularity is one of the main characteristics of hepatocellular carcinoma (HCC). However, the mechanisms of angiogenesis in HCC remain controversial. In this study, we investigate the role of Notch1 in angiogenesis of HCC. We found that Notch1 expression was correlated with formation of vasculogenic mimicry (VM) and expression of biomarkers of epithelial-to-mesenchymal transition (EMT) in the tumor specimens. Two HCC cell lines, HepG2 and MHCC97-H, with low and high Notch1 expression, respectively, were used to study the mechanism of VM formation both in vitro and in vivo. It was found that MHCC97-H cells, but not HepG2 cells form VM when they grow on matrigel in vitro. HepG2 cells gained the power of forming VM when they were overexpressed with Notch1, while knockdown Notch1 expression in MHCC97-H cells led to the loss of VM forming ability of the cells. Similar results were found in in vivo study. High expression of Notch1 in HepG2 promoted xenograft growth in nude mice, with abundant VM formation in the tumor samples. Moreover, we observed Notch1 was associated with the EMT and malignant behavior of hepatocellular carcinoma by analyzing clinical specimens, models for in vitro and in vivo experiments. HepG2 presented EMT phenomenon when induced by TGF-ß1, accompanied by Notch1 activation while MHCC97-H with knockdown of Notch1 lost the responsiveness to TGF-ß1 induction. Our results suggest that Notch1 promotes HCC progression through activating EMT pathway and forming VM. Our results will guide targeting Notch1 in new drug development.

Effects of Celastrus orbiculatus Thunb.Extract on the Overexpression of mTOR in Human HepG2 Cells / 世界科学技术-中医药现代化

This study aimed at investigating the effects of the extract of Chinese herb,Nansheteng (C.orbiculatus Thunb.),on human HepG2 cells through the overexpression of mTOR.The GV238-mTOR recombinant plasmids were transfected into HepG2 cells using molecular biological technology.The expression level of mTOR was evaluated by means of relative activity of luciferase and western blot.Human hepatic carcinoma HepG2/mTOR++ cells were treated with C.orbiculatus extract in different concentrations (20,40,80,160 and 320 tg·mL-1) for 24 h.The mTOR protein expression was detected by western blot.It was found that the protein expression of mTOR in transfected HepG2 cells was significantly enhanced.C.orbiculatus extract significantly inhibited the proliferation of HepG2/mTOR++ cells.Simultaneously,C.orbiculatus extract inhibited mTOR at its protein level in a dose-dependent manner.In conclusion,we successfully constructed recombinant mTOR cloning vectors,and established the stable HepG2 cell line with the overexpression of mTOR.Besides,C.orbiculatus extract significantly inhibited mTOR protein expression in human hepatic carcinoma HepG2 cells.

Research progress of long non-coding RNA UCA1 in tumor / 国际肿瘤学杂志

As a proto-oncogene, urothelial carcinoma antigen 1 (UCA1) is highly expressed in many human tumors such as bladder cancer, gastric cancer, breast cancer, ovarian cancer and brain glioma, which shows important application value in the diagnosis, treatment and prognosis of tumor.Studies show that UCA1 can promote tumor cell proliferation through multiple signaling pathways and molecular mechanisms, which may become a new potential target for the diagnosis and treatment of tumor.

Effect of Celastrus Orbiculatus Extract on Epithelial-Mesenchymal Transition in HepG2 Cells / 世界科学技术-中医药现代化

This study was aimed to investigate the effect of Nan-She-Teng (Celastrus orbiculatus) extract on epithe-lial-mesenchymal transition(EMT) in HepG2 cells. Except the control group, human hepatocellular carcinoma HepG2 cells in other groups were treated with Celastrus Orbiculatus extract in different concentrations (10, 20, 40, 80, and 160 μg·mL-1). The protein expression levels related to EMT were detected by western blotting. At 48 h after fertiliza-tion, the zebrafish embryos were randomly assigned to 7 groups as follows: untreated control group (E3 buffer), DMSO group (E3 buffer with 1% DMSO), and different dosages treatment of C.orbiculatus extract (10, 20, 40, 80, and 160μg·mL-1) for 24 h. The protein expressions of mTOR signaling pathways were detected by western blotting. The re-sults showed that compared with the control group, C.orbiculatus extract significantly increased E-cadherin protein expression. Simultaneously, C.orbiculatus extract inhibited vimentin and mTOR signaling pathways at protein levels. It was concluded that to a certain extent, C.orbiculatus extract prevented EMT in HepG2 cells by modulating the mTOR signaling pathway. Therefore, it suggested that mTOR can be chosen as a new therapeutic target for clinical treatment of hepatic carcinoma.